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KUBO Akiharu
Graduate School of Medicine / Faculty of Medical Sciences
Professor

Researcher basic information

■ Research Keyword
  • cell competition
  • somatic mosaicism
  • genetic disease
  • inflammatory skin disease
  • skin barrier
  • tight junction
■ Research Areas
  • Life sciences / Dermatology
  • Life sciences / Cell biology
  • Life sciences / Molecular biology
■ Committee History
  • Apr. 2014 - Present, 日本皮膚科学会, 代議員
  • 18 May 2008 - Present, 日本研究皮膚科学会, 評議員
  • 2002 - Present, 日本細胞生物学会, 評議員
  • Dec. 2015 - Dec. 2020, 日本研究皮膚科学会, 理事
  • Dec. 2014 - Dec. 2017, 日本研究皮膚科学会, 若手セミナー委員
  • 09 Dec. 2012 - 12 Dec. 2015, 日本研究皮膚科学会, 学術委員

Research activity information

■ Award
  • 2020 慶應義塾大学医学部三四会, 北里賞

  • 2019 マルホ・高木皮膚科学振興財団, マルホ・高木賞, 長島型掌蹠角化症の病態解明と治療法開発
    久保亮治

  • 2018 慶應医学会, 野村達次賞

  • 2018 日本研究皮膚科学会, JSID賞

  • 05 Jan. 2015 坂口光弘記念慶應義塾医学振興基金平成26年度慶應医学賞研究奨励賞受賞
    新年祝賀式ならびに「坂口光弘記念慶應義塾医学振興基金」に基づく慶應医学賞研究奨励賞授賞式（於慶應義塾大学病院2号館11階大会議室）にて

  • 2010 日本皮膚科学会, 平成22年度日本皮膚科学会・皆見省吾記念賞
    久保亮治
    「日本皮膚科学会皆見省吾記念賞」とは、昭和27年4月に皆見省吾先生（元九州大学名誉教授）の主催する財団法人皆見梅毒血清研究所が、皆見先生の個人的な基金をもとに性病に関する優秀な論文に対して皆見賞を授与したことが始まりです。その後、日本皮膚科学会に選考を委任し、学会事業として実施してきたことをふまえて検討した結果、平成24年には「皆見省吾記念賞」から「日本皮膚科学会皆見省吾記念賞」に名称を改めることが決定され、現在に至っております。 これまでの受賞者は81名（平成27年度現在）であり、皮膚科学においてはもっとも権威ある賞です。

  • 2010 平成22年度日本研究皮膚科学会・JSID's Fellowship SHISEIDO Award

■ Paper
  • Masatoshi Jinnin, Toshio Shimokawa, Akiko Kishi, Nobukazu Hayashi, Michiko Nagahama, Akiharu Kubo, Michio Ozeki, Shuichi Shimada, Satoshi Fukushima, Tomotaka Kawabata, Tomoki Okuyama, Aki Okubo, Yumika Sawai, Ayato Hayashi, Mana Kurimoto‐Nishiguchi, Mariko Sakata, Kayo Kunimoto, Yuki Yamamoto
    May 2025, The Journal of Dermatology
    Scientific journal

  • Kyoko Kimura, Takeshi Fukumoto, Akiharu Kubo
    May 2025, The Journal of Dermatology
    Scientific journal

  • Ayako Fukumoto, Takeshi Fukumoto, Ayumi Sato, Masahiro Oka, Akiharu Kubo
    Apr. 2025, The Journal of Dermatology
    Scientific journal

  • Akiharu Kubo
    Mar. 2025, The Journal of Dermatology
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Akiharu Kubo
    Mar. 2025, The Journal of Dermatology
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Toshihide Higashino, Mayu Konomi, Akiharu Kubo, Hiroshi Horinosono, Yoshinori Miura
    Mar. 2025, The Journal of Dermatology
    Scientific journal

  • 田原 海, 齋藤 苑子, 青木 里美, 久保 亮治
    (株)協和企画, Oct. 2024, 皮膚病診療, 46(10) (10), 924 - 927, Japanese

  • 単発のミベリ型汗孔角化症の発症原理を考察する(ビデオ上映質疑応答なし)
    久保 亮治, 齋藤 苑子
    (公社)日本皮膚科学会, Aug. 2024, 日本皮膚科学会雑誌, 134(9) (9), 2308 - 2308, Japanese

  • MVKにヘテロ接合性の病的バリアントと皮疹部表皮特異的なloss of heterozygosityを同定したporokeratosis ptychotropicaの1例
    吉岡 愛育, 福本 毅, 久保 亮治, 齋藤 苑子, 青木 里美, 中林 一彦, 臼井 駿也, 大塚 篤司
    日本皮膚科学会-大阪地方会・京滋地方会, Jun. 2024, 皮膚の科学, 23(2) (2), 151 - 151, Japanese

  • Chihiro Takemori, Michiyo Koyanagi-Aoi, Takeshi Fukumoto, Makoto Kunisada, Kazumasa Wakamatsu, Shosuke Ito, Chieko Hosaka, Seiji Takeuchi, Akiharu Kubo, Takashi Aoi, Chikako Nishigori
    Elsevier BV, Jun. 2024, Journal of Dermatological Science
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Ai Yoshioka, Yukako Shintani-Domoto, Ishino Kousuke, Akiharu Kubo, Makoto Kunisada
    Jun. 2024, The Journal of dermatology, 51(6) (6), e211-e213, English, International magazine

  • Takeshi Fukumoto, Ryo Tanaka, Rio Tanaka, Shinya Hashimoto, Ai Yoshioka, Satoshi Natsuaki, Akiharu Kubo
    Wiley, Apr. 2024, Journal of the European Academy of Dermatology and Venereology
    Scientific journal

  • Sonoko Saito, Yuki Saito, Showbu Sato, Satomi Aoki, Harumi Fujita, Yoshihiro Ito, Noriko Ono, Takeru Funakoshi, Tomoko Kawai, Hisato Suzuki, Takashi Sasaki, Tomoyo Tanaka, Masukazu Inoie, Kenichiro Hata, Keisuke Kataoka, Kenjiro Kosaki, Masayuki Amagai, Kazuhiko Nakabayashi, Akiharu Kubo
    Porokeratosis is a clonal keratinization disorder characterized by solitary, linearly arranged, or generally distributed multiple skin lesions. Previous studies showed that genetic alterations in MVK, PMVK, MVD, or FDPS-genes in the mevalonate pathway-cause hereditary porokeratosis, with skin lesions harboring germline and lesion-specific somatic variants on opposite alleles. Here, we identified non-hereditary porokeratosis associated with epigenetic silencing of FDFT1, another gene in the mevalonate pathway. Skin lesions of the generalized form had germline and lesion-specific somatic variants on opposite alleles in FDFT1, representing FDFT1-associated hereditary porokeratosis identified in this study. Conversely, lesions of the solitary or linearly arranged localized form had somatic bi-allelic promoter hypermethylation or mono-allelic promoter hypermethylation with somatic genetic alterations on opposite alleles in FDFT1, indicating non-hereditary porokeratosis. FDFT1 localization was uniformly diminished within the lesions, and lesion-derived keratinocytes showed cholesterol dependence for cell growth and altered expression of genes related to cell-cycle and epidermal development, confirming that lesions form by clonal expansion of FDFT1-deficient keratinocytes. In some individuals with the localized form, gene-specific promoter hypermethylation of FDFT1 was detected in morphologically normal epidermis adjacent to methylation-related lesions but not distal to these lesions, suggesting that asymptomatic somatic epigenetic mosaicism of FDFT1 predisposes certain skin areas to the disease. Finally, consistent with its genetic etiology, topical statin treatment ameliorated lesions in FDFT1-deficient porokeratosis. In conclusion, we identified bi-allelic genetic and/or epigenetic alterations of FDFT1 as a cause of porokeratosis and shed light on the pathogenesis of skin mosaicism involving clonal expansion of epigenetically altered cells.
    Apr. 2024, American journal of human genetics, English, International magazine
    Scientific journal

  • 岩田 浩明, 宮内 俊成, 古村 南夫, 秋山 真志, 池田 志斈, 加賀 麻弥, 川上 民裕, 久保 宜明, 久保 亮治, 澤村 大輔, 須賀 康, 乃村 俊史, 橋本 隆, 深井 和吉, 山本 明美, 米田 耕造, 家族性良性慢性天疱瘡診療ガイドライン策定委員会, 家族性良性慢性天疱瘡診療ガイドライン策定委員会
    (公社)日本皮膚科学会, Feb. 2024, 日本皮膚科学会雑誌, 134(2) (2), 273 - 287, Japanese

  • Ayaka Nakai, Deokho Lee, Yan Zhang, Chiho Shoda, Satoshi Imanishi, Heonuk Jeong, Shin-ichi Ikeda, Kazuno Negishi, Hiroyuki Nakashizuka, Satoru Yamagami, Akiharu Kubo, Toshihide Kurihara
    The early and intermediate age-related macular degeneration (AMD) is characterized by the presence of drusen and pigmentary abnormalities in the retinal pigment epithelial (RPE) cells which form the outer blood retinal barrier (oBRB). Fluid leakage through the disrupted oBRB from the choroid to the neural retina has been implicated in the pathogenesis of AMD, however; the molecular mechanisms still remain unclear. The family of four transmembrane proteins, claudins are known to form tight junctions (TJs) in the oBRB. Nonetheless, there are few reports showing how they function in the oBRB in vivo. We found that claudin-1 is dominantly expressed in TJs of the mouse RPE. To investigate the role of claudin-1 in the RPE, we generated RPE-specific Cldn1 conditional knockout mice (Best1-Cre+/- Cldn1flox/flox mice: Cldn1 cKO mice). Deficiency of Cldn1 led to age-related lipid deposits such as subretinal drusenoid deposits (SDD), increased lipid droplets in the RPE, basal lamellar deposits (BlamD) and membranous debris in the Bruch's membrane. In addition, pigmentary abnormalities such as RPE hypertrophy, multilayered-RPE cells, and ectopic pigment granules outside the RPE were observed in Cldn1 cKO mice. Our study provides new insights into the possible association of the TJ protein claudin-1 with lipid metabolism and cellular ageing in the RPE contributing to the early onset of AMD.
    Cold Spring Harbor Laboratory, Dec. 2023

  • Umi Tahara, Takeshi Matsui, Toru Atsugi, Keitaro Fukuda, Tommy W Terooatea, Aki Minoda, Akiharu Kubo, Masayuki Amagai
    The epidermis, the keratinized stratified squamous epithelium surrounding the body surface, offers a valuable framework to investigate how terrestrial animals overcome environmental stresses. However, the mechanisms underlying epidermal barrier function remain nebulous. In this study, we examined genes highly expressed in the human and mouse upper epidermis, the outer frontier that induces various barrier-related genes. Transcriptome analysis revealed that the messenger RNA level of hemoglobin α (HBA), an oxygen carrier in erythroid cells, was enriched in the upper epidermis compared with that in the whole epidermis. Immunostaining analysis confirmed HBA protein expression in human and mouse keratinocytes (KCs) of the stratum spinosum and stratum granulosum. HBA was also expressed in hair follicle KCs in the isthmus region; its expression levels were more prominent than those in interfollicular KCs. HBA expression was not observed in noncutaneous keratinized stratified squamous epithelia of mice, for example, the vagina, esophagus, and forestomach. HBA expression was upregulated in human epidermal KC cultures after UV irradiation, a major cause of skin-specific oxidative stress. Furthermore, HBA knockdown increased UV-induced production of ROS in primary KCs. Our findings suggest that epidermal HBA expression is induced by oxidative stress and acts as an antioxidant, contributing to skin barrier function.
    Dec. 2023, The Journal of investigative dermatology, 143(12) (12), 2346 - 2355, English, International magazine
    Scientific journal

  • Ayaka Ariyoshi, Takeshi Fukumoto, Shinya Imamura, Kenichiro Ohnuma, Masako Nishida, Shinya Hashimoto, Hiroshi Nagai, Akiharu Kubo
    Wiley, Sep. 2023, The Journal of Dermatology
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 【角化症を知る】角化症の遺伝学的モザイク
    久保 亮治
    (有)科学評論社, Aug. 2023, 皮膚科, 4(2) (2), 138 - 145, Japanese

  • 【汗と関連する皮膚病～診断の技量を磨く～】X連鎖性低汗性外胚葉形成不全症の女性保因者への遺伝カウンセリング
    田原 海, 青木 里美, 天谷 雅行, 久保 亮治
    (株)協和企画, Aug. 2023, 皮膚病診療, 45(8) (8), 692 - 695, Japanese

  • Keisuke Shimizu, Hideki Fujita, Daisuke Fujisawa, Koremasa Hayama, Satomi Aoki, Akiharu Kubo, Tadashi Terui
    Aug. 2023, The Journal of dermatology, 50(8) (8), e240-e242, English, International magazine

  • 母乳中に自己抗原反応性IgAが認められたNeonatal linear IgA bullous dermatosisの1例
    橋本 真哉, 福本 毅, 吉田 憲司, 堀之内 智子, 市川 裕太, 田中 悠, 藤村 順也, 野津 寛大, 石河 晃, 久保 亮治
    (公社)日本皮膚科学会, May 2023, 日本皮膚科学会雑誌, 133(5) (5), 1355 - 1355, Japanese

  • 小野 紀子, 久保 亮治
    (株)全日本病院出版会, May 2023, Derma., (334) (334), 93 - 103, Japanese

  • 寒冷刺激による増悪が示唆されたGJB3ヘテロ接合性病原性多型による変動性紅斑角皮症の1例
    齋藤 苑子, 田原 海, 小野 紀子, 青木 里美, 天谷 雅行, 佐々木 貴史, 久保 亮治
    (公社)日本皮膚科学会, Apr. 2023, 日本皮膚科学会雑誌, 133(4) (4), 709 - 709, Japanese

  • Yasuhiko Asahina, Umi Tahara, Satomi Aoki, Kazuhiko Nakabayashi, Chiharu Tateishi, Daisuke Hayashi, Masayuki Amagai, Daisuke Tsuruta, Akiharu Kubo
    A prenatal second-hit genetic change that occurs on the wild-type allele in an embryo with a congenital pathogenic variant allele results in mosaicism of monoallelic and biallelic defect of the gene, which is called superimposed mosaicism. Superimposed mosaicism of Hailey-Hailey disease (HHD) has been demonstrated in one familial case. Here, we report two unrelated HHD cases with superimposed mosaicism: a congenital monoallelic pathogenic variant of ATP2C1, followed by a postzygotic copy-neutral loss of heterozygosity. Uniquely, neither patient had a family history of HHD at the time of presentation. In the first case, the congenital pathogenic variant had occurred de novo. In the second case, the father had the pathogenic variant but had not yet developed skin symptoms. Our cases showed that superimposed mosaicism in HHD can lack a family history and that genetic analysis is crucial to classify the type of mosaicism and evaluate the risk of familial occurrence.
    Mar. 2023, European journal of human genetics : EJHG, 31(6) (6), 716 - 720, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Ayano Tanigawa, Takeshi Fukumoto, Shinya Imamura, Korefumi Nakamura, Tomonori Tanaka, Tomoo Itoh, Eiji Nakano, Chikako Nishigori, Akiharu Kubo
    Wiley, Feb. 2023, The Journal of Dermatology, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Ryo Tanaka, Yuichi Kurihara, Shohei Egami, Yasuko Saito, Takeshi Ouchi, Takeru Funakoshi, Hayato Takahashi, Noriko Umegaki-Arao, Akiharu Kubo, Akiko Tanikawa, Masayuki Amagai, Jun Yamagami
    Pemphigus and pemphigoid are autoimmune blistering diseases that affect mucosa and skin. Several clinical scoring systems, including the pemphigus disease area index (PDAI) and the bullous pemphigoid disease area index (BPDAI), have been validated for managing disease activity and severity. Current guidelines recommend that treatment response be evaluated with clinical scores and that additional second-line therapies be considered if initial treatment is insufficient for disease control. However, there have been few studies analyzing correlations between PDAI/BPDAI transitions and initial treatment effects. To investigate whether PDAI/BPDAI transitions during the treatment initiation phase correlate with initial treatment responses and whether such information can be used as a guide for necessary additional treatment, we retrospectively analyzed 67 pemphigus patients and 47 pemphigoid patients who received initial treatment at Keio University between 2012 and 2018. The clinical symptoms were evaluated weekly with PDAI/BPDAI. The patients were divided into two groups: in group A, disease was controlled only with oral corticosteroids and immunosuppressants (initial treatment), whereas in group B additional therapies were required due to insufficient responses. In pemphigus, the PDAI ratio of day 7/day 0 was significantly reduced in group A compared to group B (0.548 vs 0.761, P < 0.01) after initial treatment had started. In pemphigoid, the ratios of day 7/day 0 of BPDAI (erosion/blister) and BPDAI (urticaria/erythema) significantly decreased in group A compared to group B (0.565 vs 0.901 and 0.350 vs 0.760, respectively, P < 0.05). Receiver operating characteristic analyses on PDAI, BPDAI (erosion/blister) and BPDAI (urticaria/erythema) revealed that the cut-off values in the ratios of day 7/day 0 were 0.762, 0.675, and 0.568, respectively. Our results suggest that PDAI/BPDAI transitions during the initial phase of the treatments may be useful to predict the outcome of the treatment provided and the necessity of additional therapies to achieve disease control.
    Feb. 2023, The Journal of dermatology, 50(2) (2), 203 - 211, English, International magazine
    Scientific journal

  • Sonoko Saito, Ryo Tanaka, Noriko Ono, Noriko Umegaki-Arao, Takashi Sasaki, Satomi Aoki, Masayuki Amagai, Akiharu Kubo
    Nov. 2022, The Journal of dermatology, 49(11) (11), e405-e406, English, International magazine

  • Sonoko Saito, Noriko Ono, Takashi Sasaki, Satomi Aoki, Kenjiro Kosaki, Bunya Kuze, Kazuhiko Nakabayashi, Masayuki Amagai, Akiharu Kubo
    Pierre-Robin sequence (PRS) is a rare, congenital defect presenting with micrognathia, glossoptosis, and airway obstruction with variable inclusion of a cleft palate. Overlapping PRS with neurofibromatosis type 2 (NF2) is a syndrome caused by a chromosome 22q12 microdeletion including NF2. We describe a patient with severe early-onset NF2 overlapping with PRS that showed micrognathia, glossoptosis, and a mild form of cleft palate. We detected a de novo chromosome 22q12 microdeletion including MN1 and NF2 in the patient. Previous cases of overlapping PRS and NF2 caused by the chromosome 22q12 microdeletions showed severe NF2 phenotypes with variable severity of cleft palate and microdeletions of varying sizes. Genotype-phenotype correlations and comparison of the size and breakpoint of microdeletions suggest that some modifier genes distal to MN1 and NF2 might be linked to the cleft palate severity.
    Nov. 2022, Journal of human genetics, 67(11) (11), 675 - 678, English, International magazine
    Scientific journal

  • C. Shiiya, N. Ono, S. Aoki, M. Amagai, A. Kubo
    Oct. 2022, Journal of the European Academy of Dermatology and Venereology
    Scientific journal

  • 表皮融解性魚鱗癬モザイクにおける遺伝カウンセリングの1例
    久保 亮治, 青木 里美, 小野 紀子, 田原 海, 塩濱 愛子, 佐々木 貴史, 天谷 雅行
    日本皮膚科学会-西部支部, Oct. 2022, 西日本皮膚科, 84(5) (5), 469 - 469, Japanese

  • 後藤 芽以子, 立石 千晴, 深井 和吉, 久保 亮治, 鶴田 大輔
    (株)協和企画, Jul. 2022, 皮膚病診療, 44(7) (7), 638 - 641, Japanese

  • Hisato Iriki, Noriko Umegaki-Arao, Risa Kakuta, Harumi Fujita, Satomi Aoki, Masayuki Amagai, Takashi Sasaki, Yasuo Hamamoto, Robert Nakayama, Akiharu Kubo
    Jul. 2022, JAAD case reports, 25, 89 - 92, English, International magazine

  • アルカリ性泉への入浴後に皮疹の急性増悪をきたしたNetherton症候群の1例
    田原 海, 土屋 茉里絵, 小野 紀子, 青木 里美, 天谷 雅行, 久保 亮治
    日本皮膚科学会-西部支部, Jun. 2022, 西日本皮膚科, 84(3) (3), 264 - 264, Japanese

  • Ai Yoshioka, Makoto Kunisada, Hitoshi Fukuda, Akiharu Kubo
    May 2022, The Journal of dermatology, English, International magazine
    Link to Kobe Univ. Repository (Kernel)

  • 2型モザイクによりブラシュコ線に沿った皮疹分布を呈した小児発症ヘイリーヘイリー病の2例
    朝比奈 泰彦, 田原 海, 青木 里美, 中林 一彦, 立石 千晴, 林 大輔, 天谷 雅行, 鶴田 大輔, 久保 亮治
    (公社)日本皮膚科学会, May 2022, 日本皮膚科学会雑誌, 132(5) (5), 1310 - 1310, Japanese

  • Kimiko Nakajima, Hisato Suzuki, Mayuko Yamamoto, Tetsuya Yamamoto, Tomoko Kawai, Kazuhiko Nakabayashi, Kenichiro Hata, Kenjiro Kosaki, Hideki Nakajima, Shigetoshi Sano, Akiharu Kubo
    Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder first described by Stewart in 1977 that is characterized by severe gingival recession and periodontitis that triggers premature loss of permanent teeth and alveolar bone absorption. It was recently shown that pEDS is caused by a heterozygous missense mutation in C1R or C1S, which encode complement 1 proteases. Here, we report a familial case of pEDS with a novel heterozygous missense mutation, c.674G>C (p.R225P), in C1R (NM_001733.4). The case exhibited pretibial hyperpigmentation and extended periodontitis but neither skin extensibility nor joint hypermobility, suggesting that this mutation will expand the definition of pEDS.
    Apr. 2022, The Journal of dermatology, 49(7) (7), 714 - 718, English, International magazine
    Scientific journal

  • 田原 海, 小野 紀子, 青木 里美, 天谷 雅行, 久保 亮治
    (株)協和企画, Mar. 2022, 皮膚病診療, 44(3) (3), 232 - 235, Japanese

  • 早川 道太郎, 田原 海, 小野 紀子, 青木 里美, 中林 一彦, 久保 亮治
    (株)協和企画, Mar. 2022, 皮膚病診療, 44(3) (3), 244 - 247, Japanese

  • Hidehisa Saeki, Yuichiro Tsunemi, Satoru Arai, Susumu Ichiyama, Norito Katoh, Katsuko Kikuchi, Akiharu Kubo, Tadashi Terui, Takeshi Nakahara, Masaki Futamura, Hiroyuki Murota, Atsuyuki Igarashi
    This is the English version of guidelines for the management of asteatosis 2021 in Japan. Asteatosis is a synonym of xerosis found in a wide range of diseases that induce dry skin through impaired functions of either water retention of the stratum corneum or skin covering with acid mantle. Patients with asteatosis may be accompanied by pruritus. Moisturizers are the first-line treatment for asteatosis and their adequate use must be recommended. The main purpose of the present guidelines is to define skin symptoms requiring treatment with moisturizers for medical use in patients with asteatosis. If the deterioration of marked scaling or scratch marks is predicted, therapeutic intervention with moisturizers for medical use should be considered even in the absence of pruritus. Regarding six important points requiring decision-making in clinical practice (clinical questions), we evaluated the balance between the benefits and harm of medical interventions in reference to previous reports of clinical research, and presented the recommendation grades and evidence levels to optimize the patient outcome by medical interventions.
    Mar. 2022, The Journal of dermatology, 49(3) (3), e77-e90, English, International magazine
    Scientific journal

  • 病変部表皮特異的にNEK9の体細胞変異を認めたNevus comedonicusの2例
    田原 海, 小野 紀子, 青木 里美, 天谷 雅行, 久保 亮治, 石原 幸子, 大山 学
    (公社)日本皮膚科学会, Feb. 2022, 日本皮膚科学会雑誌, 132(2) (2), 312 - 312, Japanese

  • Eran Cohen-Barak, Wassim Azzam, Jennifer L Koetsier, Nada Danial-Farran, Moran Barcan, Maysa Hriesh, Morad Khayat, Natalia Edison, Judith Krausz, Chen Gafni-Amsalem, Akiharu Kubo, Lisa M Godsel, Michael Ziv, Stavit Allon-Shalev
    Acral peeling skin syndrome (APSS) is a heterogenous group of genodermatoses, manifested by peeling of palmo-plantar skin and occasionally associated with erythema and epidermal thickening. A subset of APSS is caused by mutations in protease inhibitor encoding genes, resulting in unopposed protease activity and desmosomal degradation and/or mis-localization, leading to enhanced epidermal desquamation. We investigated two Arab-Muslim siblings with mild keratoderma and prominent APSS since infancy. Genetic analysis disclosed a homozygous mutation in SERPINB7, c.796C > T, which is the founder mutation in Nagashima type palmo-plantar keratosis (NPPK). Although not previously formally reported, APSS was found in other patients with NPPK. We hypothesized that loss of SERPINB7 function might contribute to the peeling phenotype through impairment of keratinocyte adhesion, similar to other protease inhibitor mutations that cause APSS. Mis-localization of desmosomal components was observed in a patient plantar biopsy compared with a biopsy from an age- and gender-matched healthy control. Silencing of SERPINB7 in normal human epidermal keratinocytes led to increased cell sheet fragmentation upon mechanical stress. Immunostaining showed reduced expression of desmoglein 1 and desmocollin 1. This study shows that in addition to stratum corneum perturbation, loss of SERPINB7 disrupts desmosomal components, which could lead to desquamation, manifested by skin peeling.
    Feb. 2022, Experimental dermatology, 31(2) (2), 214 - 222, English, International magazine
    Scientific journal

  • Stephanie E. Zimmer, Takuya Takeichi, Daniel E. Conway, Akiharu Kubo, Yasushi Suga, Masashi Akiyama, Andrew P. Kowalczyk
    Dominant and recessive mutations in the desmosomal cadherin, desmoglein-1 (DSG1), cause the skin diseases palmoplantar keratoderma (PPK) and severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, respectively. Here, we compare two dominant missense mutations in the DSG1 transmembrane domain (TMD), G557R and G562R, causing PPK (DSG1PPK-TMD) and SAM syndrome (DSG1SAM-TMD), respectively, to determine the differing pathomechanisms of these mutants. Expressing the DSG1TMD mutants in a DSG-null background, we use cellular and biochemical assays to reveal differences in the mechanistic behavior of each mutant. Super resolution microscopy and functional assays showed a failure by both mutants to assemble desmosomes due to reduced membrane trafficking and lipid raft targeting. DSG1SAM-TMD maintained normal expression levels and turnover relative to DSG1WT, but DSG1PPK-TMD lacked stability, leading to increased turnover through lysosomal and proteasomal pathways and reduced expression levels. These results differentiate the underlying pathomechanisms of these disorders, suggesting that DSG1SAM-TMD acts dominant negatively while DSG1PPK-TMD is a loss-of-function mutation causing the milder PPK disease phenotype. These mutants portray the importance of the DSG TMD in desmosome function and suggest that a greater understanding of the desmosomal cadherin TMDs will further our understanding of the role that desmosomes play in epidermal pathophysiology.
    Elsevier {BV}, Feb. 2022, Journal of Investigative Dermatology, 142(2) (2), 323 - 332.e8, English, International magazine
    Scientific journal

  • Mari Minatogawa, Ai Unzaki, Hiroko Morisaki, Delfien Syx, Tohru Sonoda, Andreas R Janecke, Anne Slavotinek, Nicol C Voermans, Yves Lacassie, Roberto Mendoza-Londono, Klaas J Wierenga, Parul Jayakar, William A Gahl, Cynthia J Tifft, Luis E Figuera, Yvonne Hilhorst-Hofstee, Alessandra Maugeri, Ken Ishikawa, Tomoko Kobayashi, Yoko Aoki, Toshihiro Ohura, Hiroshi Kawame, Michihiro Kono, Kosuke Mochida, Chiho Tokorodani, Kiyoshi Kikkawa, Takayuki Morisaki, Tetsuyuki Kobayashi, Takaya Nakane, Akiharu Kubo, Judith D Ranells, Ohsuke Migita, Glenda Sobey, Anupriya Kaur, Masumi Ishikawa, Tomomi Yamaguchi, Naomichi Matsumoto, Fransiska Malfait, Noriko Miyake, Tomoki Kosho
    BACKGROUND: Musculocontractural Ehlers-Danlos syndrome is caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE). Although 48 patients in 33 families with mcEDS-CHST14 have been reported, the spectrum of pathogenic variants, accurate prevalence of various manifestations and detailed natural history have not been systematically investigated. METHODS: We collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS-CHST14 through international collaborations. RESULTS: Sixty-six patients in 48 families (33 males/females; 0-59 years), including 18 newly reported patients, were evaluated. Japanese was the predominant ethnicity (27 families), associated with three recurrent variants. No apparent genotype-phenotype correlation was noted. Specific craniofacial (large fontanelle with delayed closure, downslanting palpebral fissures and hypertelorism), skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation), cutaneous (hyperextensibility, fine/acrogeria-like/wrinkling palmar creases and bruisability) and ocular (refractive errors) features were observed in most patients (>90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>80%). Median ages at the initial episode of dislocation or large subcutaneous haematoma were both 6 years. Nine patients died; their median age was 12 years. Several features, including joint and skin characteristics (hypermobility/extensibility and fragility), were significantly more frequent in patients with mcEDS-CHST14 than in eight reported patients with mcEDS-DSE. CONCLUSION: This first international collaborative study of mcEDS-CHST14 demonstrated that the subtype represents a multisystem disorder with unique set of clinical phenotypes consisting of multiple malformations and progressive fragility-related manifestations; these require lifelong, multidisciplinary healthcare approaches.
    Nov. 2021, Journal of medical genetics, 59(9) (9), 865 - 877, English, International magazine
    Scientific journal

  • Umi Tahara, Sachiko Ishihara, Satomi Aoki, Manabu Ohyama, Akiharu Kubo
    Sep. 2021, Acta dermato-venereologica, 101(9) (9), adv00549, English, International magazine
    Scientific journal

  • 佐伯 秀久, 常深 祐一郎, 新井 達, 市山 進, 加藤 則人, 菊地 克子, 久保 亮治, 照井 正, 中原 剛士, 二村 昌樹, 室田 浩之, 五十嵐 敦之, 皮脂欠乏症診療の手引き作成委員会
    (公社)日本皮膚科学会, Sep. 2021, 日本皮膚科学会雑誌, 131(10) (10), 2255 - 2270, Japanese
    [Refereed]
    Scientific journal

  • Shohei Egami, Chihiro Suzuki, Yuichi Kurihara, Jun Yamagami, Akiharu Kubo, Takeru Funakoshi, Wataru Nishie, Kazuya Matsumura, Takahiro Matsushima, Miho Kawaida, Michiie Sakamoto, Masayuki Amagai
    IMPORTANCE: Neonatal linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare disease that can be fatal when associated with respiratory failure. All previously reported cases of neonatal LABD have been in newborns with healthy asymptomatic mothers, and the pathogenic IgA was of unknown origin. OBJECTIVE: To clarify the origin of IgA associated with LABD in neonates born of healthy asymptomatic mothers. DESIGN, SETTING, AND PARTICIPANTS: This case study analyzed the laboratory findings of a single breast-fed newborn male with neonatal LABD admitted to the Keio University Hospital in Tokyo and his healthy asymptomatic mother. The healthy newborn developed life-threatening blisters and erosions of the skin and mucous membranes on day 4 after birth. Blood serum, skin, and maternal breast milk were examined for IgA autoantibodies. MAIN OUTCOMES AND MEASURES: Histopathologic and immunofluorescence analyses of specimens (serum, skin, and breast milk) from the patient and his mother. RESULTS: Histopathologic evaluation of the newborn's skin revealed subepidermal blisters with neutrophil infiltrates, and immunofluorescence testing showed linear IgA deposition along the basement membrane zone (BMZ), which lead to the diagnosis of neonatal LABD. Indirect immunofluorescence using normal human skin after treatment with 1-mol/L sodium chloride showed the patient to have circulating IgA binding to the dermal side of BMZ. Immunohistochemical staining proved the deposition of secretory IgA in the neonatal skin by demonstrating the presence of J chain-not been seen in other LABD cases-indicating that the autoantibodies producing the blisters were derived from the maternal breast milk. Although no circulating IgA against the skin was detected in mother's sera, the breast milk contained IgA that reacted with the dermal side of the BMZ. No new blister formation was observed after cessation of breastfeeding. CONCLUSIONS AND RELEVANCE: The results of this case study suggest a passive transfer of pathogenic IgA to a newborn from an asymptomatic mother via breast milk. In prior reports, no serum from asymptomatic mothers of newborns with LABD had IgA autoantibodies binding to skin components; however, in this case, we found that the maternal breast milk contained IgA autoantibodies associated with neonatal LABD. In neonatal LABD, maternal breast milk should be examined for IgA autoantibodies and breast milk feeding should be discontinued as soon as neonatal LABD is suspected.
    Sep. 2021, JAMA dermatology, 157(9) (9), 1107 - 1111, English, International magazine
    Scientific journal

  • Kozo Yoneda, Akiharu Kubo, Toshifumi Nomura, Akemi Ishida‐Yamamoto, Yasushi Suga, Masashi Akiyama, Nobuo Kanazawa, Takashi Hashimoto
    Palmoplantar keratoderma (PPK) is a collective term for keratinizing disorders in which the main clinical symptom is hyperkeratosis on the palms and soles. To establish the first Japanese guidelines approved by the Japanese Dermatological Association for the management of PPKs, the Committee for the Management of PPKs was founded as part of the Study Group for Rare Intractable Diseases. These guidelines aim to provide current information for the management of PPKs in Japan. Based on evidence, they summarize the clinical manifestations, pathophysiologies, diagnostic criteria, disease severity determination criteria, treatment, and treatment recommendations. Because of the rarity of PPKs, there are only few clinical studies with a high degree of evidence. Therefore, several parts of these guidelines were established based on the opinions of the committee. To further optimize the guidelines, periodic revision in line with new evidence is necessary.
    Wiley, Aug. 2021, The Journal of Dermatology, 48(8) (8), e353-e367, English, International magazine
    Scientific journal

  • Umi Tahara, Masahito Yasuda, Yozo Yamada, Satomi Aoki, Showbu Sato, Masayuki Amagai, Akiharu Kubo
    FGFR3 encodes a transmembrane receptor tyrosine kinase that has six autophosphorylation sites of tyrosine. Among them, Y770 is a negative regulatory site for the downstream signaling of FGFR3. Constitutive active mutations in FGFR3 are involved in human developmental disorders including familial acanthosis nigricans, an autosomal dominant disorder characterized by general hyperpigmentation with mild acanthosis of the epidermis. Here, we report two unrelated cases of familial acanthosis nigricans with a heterozygous c.2302G>T (p.E768*) mutation in FGFR3 (NM_000142.5). FGFR3 mRNA purified from the skin lesion neither showed aberrant splicing nor nonsense-mediated mRNA decay, indicating that the FGFR3 mutant simply lacked the C-terminal 768-806 amino acids including Y770. While all of the known pathogenic mutations were missense mutations in FGFR3 showing autosomal dominant trait, the c.2302G>T mutation of FGFR3 is a unique autosomal dominant nonsense mutation that causes familial acanthosis nigricans probably via loss of negative regulatory autophosphorylation site of FGFR3.
    Springer Science and Business Media {LLC}, Aug. 2021, Journal of Human Genetics, 66(8) (8), 831 - 834, English, International magazine
    Scientific journal

  • C. Shiiya, S. Aoki, K. Nakabayashi, K. Hata, M. Amagai, A. Kubo
    Wiley, Jun. 2021, British Journal of Dermatology, 184(6) (6), 1209 - 1212
    Scientific journal

  • 栄養障害型表皮水疱症患者を対象としたレダセムチドの第2相臨床試験
    森 志朋, 外村 香子, 神尾 祥子, 政岡 安秀, 多田 由希夫, 種村 篤, 久保 亮治, 石河 晃, 藤本 学, 玉井 克人
    (公社)日本皮膚科学会, May 2021, 日本皮膚科学会雑誌, 131(5) (5), 1381 - 1381, Japanese

  • 栄養障害型表皮水疱症患者を対象としたレダセムチドの第2相臨床試験
    森 志朋, 外村 香子, 神尾 祥子, 政岡 安秀, 多田 由希夫, 種村 篤, 久保 亮治, 石河 晃, 藤本 学, 玉井 克人
    (公社)日本皮膚科学会, May 2021, 日本皮膚科学会雑誌, 131(5) (5), 1381 - 1381, Japanese

  • Satomi Aoki, Yoshiko Hirata, Tomoko Kawai, Kazuhiko Nakabayashi, Kenichiro Hata, Hisato Suzuki, Kenjiro Kosaki, Masayuki Amagai, Akiharu Kubo
    Elsevier {BV}, Apr. 2021, The Journal of investigative dermatology, 141(11) (11), 2756 - 2760, English, International magazine
    Scientific journal

  • 田原 海, 古市 祐樹, 舩越 建, 久保 亮治, 天谷 雅行, 山上 淳
    (株)協和企画, Feb. 2021, 皮膚病診療, 43(2) (2), 116 - 119, Japanese

  • Fumiyo Yasuda-Sekiguchi, Aiko Shiohama, Ayano Fukushima, Shoko Obata, Naoko Mochimaru, Aki Honda, Hiroshi Kawasaki, Akiharu Kubo, Tamotsu Ebihara, Masayuki Amagai, Takashi Sasaki
    BACKGROUND: Atopic dermatitis (AD) is heterogenous in terms of phenotype as well as genetic and environmental factors, while its associated genetic factors and pathophysiology are not fully understood. OBJECTIVE: We identify novel genetic factors enriched in a subgroup of AD patients with characteristic clinical features. METHODS: We clinically subgrouped 18 AD patients who exhibited distinctive characteristic of persistent skin eruption areas on the face and neck from 92 Japanese adult AD patients and identified disease-associated genetic factors enriched within the subgroup. Targeted resequencing and subsequent genetic association analyses were used to identify novel enriched genetic variations in the subgroup compared with the other AD patients. RESULTS: Targeted resequencing of 648 skin associated genes revealed an enrichment of 12 single nucleotide variations (SNVs) in patients with face and neck AD (n = 18) compared with the general Japanese population in the database. Subsequent allele frequency comparison between the face and neck AD and non - face and neck AD subgroups revealed enrichment of five SNVs. Multivariate analysis using genotype data revealed that three SNVs in theTLR1, TIRAP, and PSAPL1 genes, two of the three genes are involved in the Toll-like receptor pathway, were significantly enriched in patients with face and neck AD. CONCLUSION: These findings revealed that the SNVs in genes associated with the innate immune pathway are enriched in a subgroup of AD. The combinational approach of clinical subgrouping and genotyping is valuable for detecting novel disease-associated genetic factors.
    Feb. 2021, Journal of dermatological science, 101(2) (2), 93 - 100, English, International magazine
    Scientific journal

  • 治療抵抗性のカンジダ性肉芽腫を広範囲に生じたKID症候群の1例
    八代 望, 田原 海, 朝比奈 泰彦, 小野 紀子, 久保 亮治
    (公社)日本皮膚科学会, Jan. 2021, 日本皮膚科学会雑誌, 131(1) (1), 137 - 137, Japanese

  • Michitaro Hayakawa, Umi Tahara, Noriko Ono, Satomi Aoki, Tomoko Kawai, Kazuhiko Nakabayashi, Kenichiro Hata, Masayuki Amagai, Akiharu Kubo
    Wiley, Dec. 2020, The Journal of dermatology, 47(12) (12), e453-e454, English, International magazine
    Scientific journal

  • Harumi Fujita, Takashi Sasaki, Tatsuo Miyamoto, Silvia Natsuko Akutsu, Showbu Sato, Takehiko Mori, Kazuhiko Nakabayashi, Kenichiro Hata, Hisato Suzuki, Kenjiro Kosaki, Shinya Matsuura, Yoichi Matsubara, Masayuki Amagai, Akiharu Kubo
    Damage to the genome can accelerate aging. The percentage of aneuploid cells, that is, cells with an abnormal number of chromosomes, increases during aging; however, it is not clear whether increased aneuploidy accelerates aging. Here, we report an individual showing premature aging phenotypes of various organs including early hair loss, atrophic skin, and loss of hematopoietic stem cells; instability of chromosome numbers known as mosaic variegated aneuploidy (MVA); and spindle assembly checkpoint (SAC) failure. Exome sequencing identified a de novo heterozygous germline missense mutation of c.856C>A (p.R286S) in the mitotic activator CDC20. The mutant CDC20 showed lower binding affinity to BUBR1 during the formation of the mitotic checkpoint complex (MCC), but not during the interaction between MCC and the anaphase-promoting complex/cyclosome (APC/C)-CDC20 complex. While heterozygous knockout of CDC20 did not induce SAC failure, knock-in of the mutant CDC20 induced SAC failure and random aneuploidy in cultured cells, indicating that the particular missense mutation is pathogenic probably via the resultant imbalance between MCC and APC/C-CDC20 complex. We postulate that accelerated chromosome number instability induces premature aging in humans, which may be associated with early loss of stem cells. These findings could form the basis of a novel disease model of the aging of the body and organs.
    Nov. 2020, Aging cell, 19(11) (11), e13251, English, International magazine
    Scientific journal

  • Umi Tahara, Noriko Ono, Satomi Aoki, Tomoko Kawai, Kazuhiko Nakabayashi, Kenichiro Hata, Masayuki Amagai, Akiharu Kubo
    Wiley, Nov. 2020, The Journal of dermatology, 47(11) (11), e393-e394, English, International magazine
    Scientific journal

  • Noriko Umegaki‐Arao, Sae Tanemoto, Keiji Tanese, Akiharu Kubo, Hayato Takahashi, Yuichi Kurihara, Erika Yanagisawa, Kaori Kameyama, Masayuki Amagai, Masataka Saito
    Wiley, Oct. 2020, The Journal of Dermatology, 47(10) (10), e357-e359, English, International magazine
    Scientific journal

  • Naoki Oiso, Akiharu Kubo, Akira Shimizu, Hisato Suzuki, Kenjiro Kosaki, Takaaki Chikugo, Kazuhiko Nakabayashi, Kenichiro Hata, Shigeto Yanagihara, Osamu Ishikawa, Yoichi Matsubara, Masayuki Amagai, Akira Kawada
    Sep. 2020, International journal of dermatology, 59(9) (9), e334-e336, English, International magazine

  • Kenji Yoshida, Mayuko Kobayashi, Yukiko Matsunaga, Akiharu Kubo, Akira Ishiko
    Wiley, Jul. 2020, The Journal of dermatology, English, International magazine
    Scientific journal

  • 高熱、皮膚粘膜症状、ぶどう膜炎で初発したBehcet病の2例
    新川 宏樹, 田中 諒, 田原 海, 朱 瀛瑤, 種瀬 啓士, 舩越 建, 久保 亮治, 太田 優, 永井 紀博, 天谷 雅行, 谷川 瑛子
    日本皮膚科学会-西部支部, Jun. 2020, 西日本皮膚科, 82(3) (3), 231 - 231, Japanese

  • 18番染色体長腕の片親性ダイソミーによりSERPINB7 c.796C>T変異がホモ接合となって発症した長島型掌蹠角化症の1例
    早川 道太郎, 田原 海, 小野 紀子, 青木 里美, 天谷 雅行, 久保 亮治, 河合 智子, 中林 一彦
    (公社)日本皮膚科学会, Mar. 2020, 日本皮膚科学会雑誌, 130(3) (3), 410 - 410, Japanese

  • Thyssen JP, Jakasa I, Riethmuller C, Schon MP, Braun A, Haftek M, Fallon PG, Wroblewski J, Jakubowski H, Eckhart L, Declercq W, Koppes S, Engebretsen KA, Bonefeld C, Irvine AD, Keita-Alassane S, Simon M, Kawasaki H, Kubo A, Amagai M, Matsui T, Kezic S
    Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp-/-), filaggrin (Flgft/ft and Flg-/-), filaggrin-hornerin (FlgHrnr-/-), and bleomycin hydrolase (Blmh-/-) were investigated. Sasp-/- and Flg-/- were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp-/-. Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.
    Mar. 2020, J Invest Dermatol, 140(3) (3), 615 - 623 e5, English, International magazine
    [Refereed]
    Scientific journal

  • Atsugi T, Yokouchi M, Hirano T, Hirabayashi A, Nagai T, Ohyama M, Abe T, Kaneko M, Zouboulis CC, Amagai M, Kubo A
    Holocrine secretion is a specific mode of secretion involving secretion of entire cytoplasmic materials with remnants of dead cells, as observed in multicellular exocrine glands of reptiles, birds, and mammals. Here, we found that sebaceous glands in mice, representative of multicellular exocrine glands of mammals, exhibit a form of polarized stratified epithelium equipped with tight junctions (TJs), and found that holocrine secretion occurred outside the TJ barriers. Sebaceous glands share characteristics of stratified epithelia with interfollicular epidermis, including basal-layer-restricted cell proliferation, TJ barrier formation at a specific single layer of cells with apico-basolateral plasma membrane polarity, and cell death outside the TJ barrier. Knockout of claudin-1, a transmembrane adhesive protein in TJs, in mice caused leakage of the TJ barrier in sebaceous glands and incomplete degradation of the plasma membrane and nuclei during holocrine secretion. Claudin-1 knockout resulted in the accumulation of incompletely degenerated sebocytes in sebaceous ducts, suggesting that the TJ barrier was necessary for differentiation of holocrine secretion. The redefinition of sebaceous glands as TJ-forming stratified epithelia provides an important framework to understand the molecular mechanism of holocrine secretion.
    Feb. 2020, J Invest Dermatol, 140(2) (2), 298 - 308 e5, English, International magazine
    [Refereed]
    Scientific journal

  • Mukai M, Kurihara Y, Ito Y, Shintani Y, Takahashi H, Kubo A, Amagai M, Umegaki-Arao N
    Wiley, Jan. 2020, J Dermatol, 47(1) (1), e26 - e28, English, International magazine
    [Refereed]
    Scientific journal

  • ダーモスコピーにて橙黄色領域に蛇行状血管がみられた皮膚限局性結節性アミロイドーシスの1例
    八谷美穂, 小松広彦, 久保亮治, 永井俊弘, 田中勝, 布袋祐子
    Nov. 2019, 臨床皮膚科, 73(12) (12), 978 - 982, Japanese
    [Refereed]

  • Fukuchi K, Tatsuno K, Sakaguchi K, Sano S, Sasaki T, Aoki S, Kubo A, Tokura Y
    Wiley, Nov. 2019, J Dermatol, 46(11) (11), e416 - e418, English, International magazine
    [Refereed]
    Scientific journal

  • Saito S, Tanaka R, Sasaki T, Aoki S, Yasuhara R, Nakayama Y, Nagai T, Sonobe H, Ozawa Y, Kubo A
    Wiley, Oct. 2019, The Journal of dermatology, 47(1) (1), e18-e20, English, International magazine
    Scientific journal

  • Akiharu Kubo, Daisuke Yamada
    Massachusetts Medical Society, Oct. 2019, New England Journal of Medicine, 381(15) (15), 1458 - 1458
    Scientific journal

  • Takahashi S, Ishida A, Kubo A, Kawasaki H, Ochiai S, Nakayama M, Koseki H, Amagai M, Okada T
    The epidermal barrier is thought to protect sensory nerves from overexposure to environmental stimuli, and barrier impairment leads to pathological conditions associated with itch, such as atopic dermatitis (AD). However, it is not known how the epidermal barrier continuously protects nerves for the sensory homeostasis during turnover of the epidermis. Here we show that epidermal nerves are contained underneath keratinocyte tight junctions (TJs) in normal human and mouse skin, but not in human AD samples or mouse models of chronic itch caused by epidermal barrier impairment. By intravital imaging of the mouse skin, we found that epidermal nerve endings were frequently extended and retracted, and occasionally underwent local pruning. Importantly, the epidermal nerve pruning took place rapidly at intersections with newly forming TJs in the normal skin, whereas this process was disturbed during chronic itch development. Furthermore, aberrant Ca2+ increases in epidermal nerves were induced in association with the disturbed pruning. Finally, TRPA1 inhibition suppressed aberrant Ca2+ increases in epidermal nerves and itch. These results suggest that epidermal nerve endings are pruned through interactions with keratinocytes to stay below the TJ barrier, and that disruption of this mechanism may lead to aberrant activation of epidermal nerves and pathological itch.
    Jun. 2019, Sci Rep, 9(1) (1), 8625 - 8625, English, International magazine
    [Refereed]
    Scientific journal

  • Kubo A, Sasaki T, Suzuki H, Shiohama A, Aoki S, Sato S, Fujita H, Ono N, Umegaki-Arao N, Kawai T, Nakabayashi K, Hata K, Yamada D, Matsubara Y, Kosaki K, Amagai M
    Patients with disseminated superficial actinic porokeratosis (DSAP) and linear porokeratosis (LP) exhibit monoallelic germline mutations in genes encoding mevalonate pathway enzymes, such as MVD or MVK. Here, we showed that each skin lesion of DSAP exhibited an individual second hit genetic change in the wild-type allele of the corresponding gene specifically in the epidermis, indicating that a postnatal second hit triggering biallelic deficiency of the gene is required for porokeratosis to develop. Most skin lesions exhibited one of two principal second hits, either somatic homologous recombinations rendering the monoallelic mutation biallelic or C>T transition mutations in the wild-type allele. The second hits differed among DSAP lesions but were identical in those of congenital LP, suggesting that DSAP is attributable to sporadic postnatal second hits and congenital LP to a single second hit in the embryonic period. In the characteristic annular skin lesions of DSAP, the central epidermis featured mostly second hit keratinocytes, and that of the annular ring featured a mixture of such cells and naïve keratinocytes, implying that each lesion reflects the clonal expansion of single second hit keratinocytes. DSAP is therefore a benign intraepidermal neoplasia, which can be included in the genetic tumor disorders explicable by Knudson's two-hit hypothesis.
    Elsevier {BV}, Jun. 2019, The Journal of investigative dermatology, 139(12) (12), 2458 - 2466.e9, English, International magazine
    [Refereed]
    Scientific journal

  • Lewis JD, Caldara AL, Zimmer SE, Stahley SN, Seybold A, Strong NL, Frangakis AS, Levental I, Wahl JK, Mattheyses AL, Sasaki T, Nakabayashi K, Hata K, Matsubara Y, Ishida-Yamamoto A, Amagai M, Kubo A, Kowalczyk AP
    Desmogleins (Dsgs) are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft association. Further, we identify a novel mutation in the DSG1 TMD (G562R) that causes severe dermatitis, multiple allergies, and metabolic wasting syndrome. Molecular modeling predicts that this G-to-R mutation shortens the DSG1 TMD, and experiments directly demonstrate that this mutation compromises both lipid raft association and desmosome incorporation. Finally, cryo-electron tomography indicates that the lipid bilayer within the desmosome is ∼10% thicker than adjacent regions of the plasma membrane. These findings suggest that differences in bilayer thickness influence the organization of adhesion molecules within the epithelial plasma membrane, with cadherin TMDs recruited to the desmosome via the establishment of a specialized mesoscale lipid raft-like membrane domain.
    Jun. 2019, Molecular biology of the cell, 30(12) (12), 1390 - 1405, English, International magazine
    [Refereed]
    Scientific journal

  • Keiko Usui, Nanako Kadono, Yuki Furuichi, Keiichiro Shiraga, Takashi Saitou, Hiroshi Kawasaki, Kiminori Toyooka, Hiroomi Tamura, Akiharu Kubo, Masayuki Amagai, Takeshi Matsui
    Jun. 2019, Journal of dermatological science, 94(3) (3), 346 - 349, English, International magazine
    [Refereed]

  • 妊娠中に急激に増大した隆起性皮膚線維肉腫の1例
    豊島 進, 栗原 佑一, 持丸 奈央子, 平井 郁子, 中村 善雄, 久保 亮治, 天谷 雅行, 舩越 建
    ＜文献概要＞41歳,女性.初診1年前から左季肋部に結節を自覚した.妊娠15週頃から急速に増大し,妊娠17週時に当科を受診した.初診時,表面に紫斑を伴う4cm大の弾性軟の腫瘤を認めた.超音波検査で血管に富む境界明瞭な腫瘤であり,血管腫を疑い局所麻酔下で全摘術を行った.病理組織学的に,真皮から皮下に境界明瞭で血管に富む腫瘍を認めた.構成する細胞は紡錘形の細胞で,花むしろ状配列をなしてびまん性に増殖していた.核の大小不同や分裂像は目立たなかった.免疫組織化学染色ではCD34陽性,FISH法で第17染色体COL1A1遺伝子座と第22染色体PDGFB遺伝子座の転座が示唆された.隆起性皮膚線維肉腫と診断し,妊娠24週時に全身麻酔で筋膜を含め追加切除した.この腫瘍は以前にも妊娠中に急激に増大する腫瘍として報告されている.経過観察中に増大すると手術の侵襲が大きくなることや,転移の可能性もあるため,妊婦に生じた腫瘤における重要な鑑別疾患と考えられた.
    (株)医学書院, May 2019, 臨床皮膚科, 73(6) (6), 451 - 456, Japanese

  • Nishihara K, Tohyama M, Kubo A
    © 2019 The Authors. Pediatric Dermatology Published by Wiley Periodicals, Inc. Woolly hair nevus is a rare syndrome that presents as woolly hair in restricted areas of the scalp and may be associated with pigmented macules or epidermal nevus on the body. Here, we report a case of woolly hair nevus, linear pigmentation, and multiple epidermal nevi with a somatic HRAS c.34G>A(p.G12S) mutation.
    Pediatric Dermatology, May 2019, Pediatr Dermatol, 36(3) (3), 368 - 371, English
    [Refereed]

  • Yoshida K, Sadamoto M, Sasaki T, Kubo A, Ishiko A
    Journal of Dermatology, Feb. 2019, Journal of Dermatology, 46(2) (2), e61 - e63, English, International magazine

  • PET-CTで患側膝部に滑膜炎による異常集積を認めた病期IIIC第2趾悪性黒色腫の1例
    雪野祐莉子, 栗原佑一, 八代聖, 久保亮治, 安西秀美, 菊田一貴, 森岡秀夫, 川井田みほ, 舩越建
    Jan. 2019, 臨床皮膚科, 73(1) (1), 65 - 70, Japanese
    [Refereed]

  • Interstitial granulomatous dermatitisとpalisading neutrophilic granulomatous dermatitisの両疾患の病理組織学的特徴を示した多発肉芽腫性丘疹の1例
    入來景悟, 佐藤美聡, 三上修治, 奥田恭章, 久保亮治
    Dec. 2018, 臨床皮膚科, 72(13) (13), 1057 - 1062, Japanese
    [Refereed]

  • Ryo Tanaka, Noriko Umegaki‐Arao, Takashi Sasaki, Satomi Aoki, Kazue Yoshida, Hironori Niizeki, Akiharu Kubo
    Wiley, Nov. 2018, The Journal of Dermatology, 45(11) (11), e302 - e303, English
    [Refereed]
    Scientific journal

  • Chiaki Murase, Takuya Takeichi, Akitaka Shibata, Masahiro Nakatochi, Fumie Kinoshita, Akiharu Kubo, Kimiko Nakajima, Norito Ishii, Hiroo Amano, Koji Masuda, Hiroshi Kawakami, Takuro Kanekura, Ken Washio, Masayuki Asano, Kazuya Teramura, Eijiro Akasaka, Mikiko Tohyama, Yutaka Hatano, Toyoko Ochiai, Shinichi Moriwaki, Tomotaka Sato, Akemi Ishida-Yamamoto, Mariko Seishima, Michiko Kurosawa, Shigaku Ikeda, Masashi Akiyama
    BACKGROUND: Congenital ichthyoses (CIs) adversely affect quality of life (QOL) in patients. However, the effects of CIs on patient QOL have not been studied sufficiently. OBJECTIVE: To investigate the association between disease severity and QOL in patients with harlequin ichthyosis (HI) and ichthyosis: syndromic forms (ISFs) METHODS: Clinical information of patients with HI and ISFs from 2010 to 2015 were obtained from 100 dermatology departments/divisions of principal institutes/hospitals throughout Japan. We examined the relationship between disease severity and QOL in patients with HI and ISFs. Patients who were aged 8 years or older and participated in a multicenter retrospective questionnaire survey in Japan were assessed by dermatology life quality index (DLQI, range of 0-30) and clinical ichthyosis score (range of 0-100). RESULTS: Netherton syndrome patients had a significantly higher risk of allergy to food or environmental allergens than patients with other phenotypes. Keratitis-ichthyosis-deafness (KID) syndrome patients showed a significantly higher risk of skin infections than patients with other phenotypes. Complete data on DLQI were obtained from 13 patients, whose median age was 21 (8-71) years. Nine patients were male, and 4 were female. Systemic retinoids were administrated to 2 of the 3 HI patients. The Spearman's correlation coefficient between the clinical ichthyosis score and DLQI was 0.611 (P < 0.05). CONCLUSION: We confirmed that Netherton syndrome and KID syndrome patients have a higher risk of allergy to food or environmental allergens and of skin infections, respectively. QOL impairment correlates with disease severity in HI and ISFs patients.
    Journal of Dermatological Science, Nov. 2018, Journal of dermatological science, 92(2) (2), 127 - 133, English, International magazine
    [Refereed]
    Scientific journal

  • Nomura H, Kurihara Y, Saito M, Fukushima A, Shintani Y, Shiiyama R, Toshima S, Kamata A, Yamagami J, Funakoshi T, Kameyama K, Amagai M, Kubo A, Umegaki-Arao N
    Oct. 2018, J Eur Acad Dermatol Venereol, 32(10) (10), e386 - e389
    [Refereed]

  • Kenta Kobayashi, Keiji Tanese, Akiharu Kubo, Naoko Matsumoto-Mochimaru, Aya Sasaki, Kaori Kameyama, Masayuki Amagai, Noriko Umegaki-Arao
    Human papillomavirus (HPV) has been detected in some cases of Bowen's disease, particularly on the fingers and genitalia. HPV-58 is classified as a high-risk mucosal type and accounts for a high percentage of cervical cancer in Asia. Moreover, several HPV-58 lineages, including sublineage A1, have a high prevalence in Asia. However, the nature of HPV-58-associated skin cancer is still unknown. Here, we report a case of a Japanese patient with multiple Bowen's disease on the fingers. A 33-year-old man presented with multiple reddish-brown scaly plaques on his left middle finger and right ring finger. All lesions were surgically excised, and the diagnosis of Bowen's disease was made. We performed Sanger sequencing using DNA extracted from paraffin-embedded samples and identified HPV-58 sublineage A1. Additionally, we review previous reports on HPV-58-associated skin cancers, including our case, showing a high regional prevalence in Asia. Further studies would be needed to reveal the relationship between HPV-58 lineages and carcinogenesis in the skin.
    Journal of Dermatology, Oct. 2018, The Journal of dermatology, 45(10) (10), 1195 - 1198, English, International magazine
    [Refereed]
    Scientific journal

  • Yokouchi M, Kubo A
    © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd The skin forms a life-sustaining barrier between the organism and the physical environment. The physical barrier of the skin is mainly comprised of the stratum corneum (SC) and tight junctions (TJs). In recent years, there have been significant advances in our understanding of the epidermal TJ function, composition and regulation. In contrast to the SC, TJs are highly dynamic structures. It was discovered that spatiotemporal regulation of dynamic TJ replacement from cell to cell maintains the TJ barrier homeostasis of the skin, despite continuous cellular turnover. This review summarizes current knowledge about how TJ barrier homeostasis is maintained in simple and stratified epithelia, and how diseases and other conditions affect the TJ barrier in the skin.
    Experimental Dermatology, Aug. 2018, Exp Dermatol, 27(8) (8), 876 - 883, English

  • 多発する被角血管腫から疑われたFabry病の1例
    柳澤 絵里加, 田中 諒, 大内 結, 久保 亮治, 山上 淳, 徳山 博文, 脇野 修, 伊藤 裕
    (公社)日本皮膚科学会, Jul. 2018, 日本皮膚科学会雑誌, 128(8) (8), 1668 - 1668, Japanese

  • Watanuki, S, Fujita, H, Kouyama, K, Amagai, M, Kubo, A
    BACKGROUND: Centrosomes contain two centrioles: a pre-existing mature centriole and a newly formed immature centriole. Each centriole is duplicated once within a cell cycle, which is crucial for proper centrosome duplication and cell division. OBJECTIVE: To describe the centrosome duplication cycle in human epidermis, Bowen's disease (BD), and squamous cell carcinoma (SCC). METHODS: Immunofluorescent staining of centriolar proteins and Ki-67 was used to evaluate cell cycles and the number of centrioles. Centrobin and Outer dense fiber of sperm tails 2 (ODF2) were used as markers for immature and mature centrioles, respectively. RESULTS: Normal human primary epidermal keratinocytes in a monolayered culture have one centrobin(+) centriole (CTRB(1+) cells) supposed in G0/G1 phases or have two centrobin(+) centrioles (CTRB(2+) cells) supposed in S-G2 phase. In a three-dimensional culture and in vivo human epidermis, the majority of suprabasal cells were CTRB(2+) cells, in spite of their non-proliferative Ki-67(-) nature. The tumor mass of BD and SCC contained CTRB(1+) cells and Ki-67(+) proliferating and Ki-67(-) non-proliferative CTRB(2+) cells. Clumping cells in BD had increased numb
    Journal of Dermatological Science, Jul. 2018, J Dermatol Sci, 91(1) (1), 9 - 18, English, International magazine
    [Refereed]
    Scientific journal

  • Saori Watanuki, Harumi Fujita, Keisuke Kouyama, Masayuki Amagai, Akiharu Kubo
    Elsevier Ireland Ltd, Jul. 2018, Journal of Dermatological Science, 91(1) (1), 9 - 18, English
    [Refereed]
    Scientific journal

  • Toshiaki Kogame, Yo Kaku, Yuichiro Endo, Chisato Yamashita, Ayumi Horiguchi, Akiharu Kubo, Kenji Kabashima
    John Libbey Eurotext, Jul. 2018, European Journal of Dermatology, 28(4) (4), 519 - 520, English
    [Refereed]
    Scientific journal

  • Takuji Masunaga, Akiharu Kubo, Akira Ishiko
    Blackwell Publishing Ltd, Jun. 2018, Journal of Dermatology, 45(6) (6), 742 - 745, English
    [Refereed]
    Scientific journal

  • H. Horikawa, Y. Kurihara, T. Funakoshi, N. Umegaki-Arao, H. Takahashi, A. Kubo, A. Tanikawa, N. Kodani, Y. Minami, S. Meguro, H. Itoh, K. Izumi, W. Nishie, H. Shimizu, M. Amagai, J. Yamagami
    Blackwell Publishing Ltd, Jun. 2018, British Journal of Dermatology, 178(6) (6), 1462 - 1463, English
    [Refereed]

  • Aiko Yamauchi, Akiharu Kubo, Noriko Ono, Aiko Shiohama, Daisuke Tsuruta, Kazuyoshi Fukai
    Blackwell Publishing Ltd, May 2018, Journal of Dermatology, 45(5) (5), e112 - e113, English
    [Refereed]
    Scientific journal

  • Miho Mukai, Harumi Fujita, Noriko Umegaki-Arao, Takashi Sasaki, Fumiyo Yasuda-Sekiguchi, Tsuyoshi Isojima, Sachiko Kitanaka, Masayuki Amagai, Akiharu Kubo
    Elsevier Ireland Ltd, Apr. 2018, Journal of Dermatological Science, 90(1) (1), 90 - 93, English
    [Refereed]

  • Yoshie Fukunaga, Akiharu Kubo, Takashi Sasaki, Daisuke Tsuruta, Kazuyoshi Fukai
    Blackwell Publishing Ltd, Apr. 2018, Journal of Dermatology, 45(4) (4), e72 - e73, English
    [Refereed]
    Scientific journal

  • Kensuke Fukuchi, Kazuki Tatsuno, Kayo Matsushita, Akiharu Kubo, Taisuke Ito, Yoshiki Tokura
    Blackwell Publishing Ltd, Feb. 2018, Journal of Dermatology, 45(2) (2), 207 - 210, English
    [Refereed]
    Scientific journal

  • 皮膚バリアとアトピー性皮膚炎 表皮細胞のかたちと視点から
    横内麻里子, 久保 亮治
    Feb. 2018, 細胞, 50(2) (2), 60 - 62, Japanese

  • アトピー性皮膚炎とフィラグリン
    川崎洋, 久保 亮治
    Dec. 2017, 小児科臨床, 70(12) (12), 1961 - 1968, Japanese

  • Keiji Tanese, Hironori Niizeki, Atsuhito Seki, Kazuhiko Nakabayashi, Shinsuke Nakazawa, Yoshiki Tokura, Yuhei Kawashima, Akiharu Kubo, Akira Ishiko
    Nov. 2017, JOURNAL OF DERMATOLOGY, 44(11) (11), 1320 - 1321, English
    [Refereed]

  • Matthias Ruebsam, Aaron F. Mertz, Akiharu Kubo, Susanna Marg, Christian Juengst, Gladiola Goranci-Buzhala, Astrid C. Schauss, Valerie Horsley, Eric R. Dufresne, Markus Moser, Wolfgang Ziegler, Masayuki Amagai, Sara A. Wickstroem, Carien M. Niessen
    Nov. 2017, NATURE COMMUNICATIONS, 8(1) (1), 1250, English
    [Refereed]
    Scientific journal

  • 手掌足蹠の悪臭を訴えた長島型掌蹠角化症の1例
    林大輔, 深井和吉, 塩濱愛子, 久保 亮治, 格谷敦子, 鶴田大輔
    Nov. 2017, 日本小児皮膚科学会雑誌, 36(3) (3), 190 - 193, Japanese

  • Susumu Ichiyama, Akiharu Kubo, Takemitsu Matayoshi, Hidehisa Saeki, Yoko Funasaka
    Oct. 2017, JOURNAL OF DERMATOLOGY, 44(10) (10), E250 - E251, English
    [Refereed]

  • 骨髄異形成症候群に生じた骨髄性プロトポルフィリン症の1例
    山本紗規子, 吉田哲也, 齊藤優子, 佐々木優, 矢野優美子, 井口豊崇, 久保 亮治, 佐藤友隆
    医学書院, Sep. 2017, 臨床皮膚科, 71(10) (10), 837 - 841, Japanese

  • Misaki Kinoshita-Ise, Yoshio Nakamura, Yoshiko Kumagai, Akiharu Kubo, Keisuke Nagao, Takeru Funakoshi
    Aug. 2017, JOURNAL OF DERMATOLOGY, 44(8) (8), 973 - 975, English
    [Refereed]

  • 皮膚バリア、最近の進歩 ケルビン14面体モデル
    Akiharu Kubo
    Aug. 2017, 皮膚病診療, 39(8) (8), 808 - 813, Japanese

  • Katsuno, M, Shiohama, A, Aoki, S, Kitamura, H, Sasaki, T, Amagai, M, Kubo, A
    Jul. 2017, J Dermatol, 44(7) (7), e146 - e147, English, International magazine

  • Masako Katsuno, Aiko Shiohama, Satomi Aoki, Hajime Kitamura, Tetsuo Sasaki, Masayuki Amagai, Akiharu Kubo
    Jul. 2017, JOURNAL OF DERMATOLOGY, 44(7) (7), E146 - E147, English
    [Refereed]

  • Kimiko Nakajima, Mayuko Ishiguro, Aiko Shiohama, Akiharu Kubo, Shigetoshi Sano
    Jul. 2017, JOURNAL OF DERMATOLOGY, 44(7) (7), 841 - 843, English
    [Refereed]

  • Honda, A, Umegaki-Arao, N, Sasaki, T, Nakabayashi, K, Hata, K, Matsubara, Y, Tanikawa, A, Amagai, M, Kubo, A
    Jun. 2017, J Dermatol, 44(6) (6), e109 - e110, English, International magazine

  • Akimasa Adachi, Mayumi Komine, Takeo Maekawa, Satoru Murata, Aiko Shiohama, Akiharu Kubo, Mamitaro Ohtsuki
    Jun. 2017, ACTA DERMATO-VENEREOLOGICA, 97(6) (6), 756 - 758, English
    [Refereed]

  • Aki Honda, Noriko Umegaki-Arao, Takashi Sasaki, Kazuhiko Nakabayashi, Kenichiro Hata, Yoichi Matsubara, Akiko Tanikawa, Masayuki Amagai, Akiharu Kubo
    Jun. 2017, JOURNAL OF DERMATOLOGY, 44(6) (6), E109 - E110, English
    [Refereed]

  • 爪乾癬の診断と治療法に関する検討
    福田 理紗, 種本 紗枝, 茶谷 彩華, 梅垣 知子, 久保 亮治, 天谷 雅行, 斉藤 昌孝
    (公社)日本皮膚科学会, May 2017, 日本皮膚科学会雑誌, 127(6) (6), 1372 - 1372, Japanese

  • Kumagai, Y, Umegaki-Arao, N, Sasaki, T, Nakamura, Y, Takahashi, H, Ashida, A, Tsunemi, Y, Kawashima, M, Shimizu, A, Ishiko, A, Nakamura, K, Tsuchihashi, H, Amagai, M, Kubo, A
    May 2017, J Eur Acad Dermatol Venereol, 31(5) (5), e241 - e243

  • Y. Kumagai, N. Umegaki-Arao, T. Sasaki, Y. Nakamura, H. Takahashi, A. Ashida, Y. Tsunemi, M. Kawashima, A. Shimizu, A. Ishiko, K. Nakamura, H. Tsuchihashi, M. Amagai, A. Kubo
    May 2017, JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 31(5) (5), e241 - e243, English
    [Refereed]
    Scientific journal

  • 遺伝外来における診療と遺伝カウンセリング
    Akiharu Kubo
    May 2017, 臨床皮膚科, 71(6) (6), 386 - 387, Japanese

  • Umegaki-Arao, N, Sasaki, T, Fujita, H, Aoki, S, Kameyama, K, Amagai, M, Seishima, M, Kubo, A
    Apr. 2017, J Invest Dermatol, 137(4) (4), 967 - 970, English, International magazine

  • Noriko Umegaki-Arao, Takashi Sasaki, Harumi Fujita, Satomi Aoki, Kaori Kameyama, Masayuki Amagai, Mariko Seishima, Akiharu Kubo
    Apr. 2017, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 137(4) (4), 967 - 970, English
    [Refereed]

  • 小野紀子, 松井順子, 小崎健次郎, 田中勝, 天谷雅行, 久保亮治

    Pallister-Killian syndrome is caused by mosaic tetrasomy 12p; the clinical features are hypomelanotic streaks along Blaschko's lines, temporal and frontal balding with woolly hair, overgrowth, and psychomotor retardation. Herein we report a case of Pallister-Killian syndrome and discuss the clinical definition of hypomelanosis of Ito, which is now considered to be general term for mosaicism showing streaks of hypopigmentation along Blaschko's line and psychomotor retardation.

    Japanese Dermatological Association, Mar. 2017, 日本皮膚科学会雑誌, 127(3) (3), 455 - 461, Japanese

  • 熊谷宜子, 梅垣知子, 久保亮治
    Feb. 2017, Visual Dermatology, 16(3) (3), 267 - 269, Japanese

  • 高橋 苑子, 石田 梓, 川崎 洋, 久保 亮治, 天谷 雅行, 岡田 峰陽

      アトピー性皮膚炎において，慢性的な痒みは症状の悪化に大きく関与している．近年，角質やタイトジャンクションなどの皮膚バリアの機能不全が，痒みの発生に関与していると考えられている．しかしながら，痒みを担う皮膚神経の活性化がどこでどのように起こっているかは明らかにされていない．本研究では，新たに確立した三次元ホールマウント免疫染色法を用いて，正常マウス及びアトピー性皮膚炎モデルマウスの，表皮タイトジャンクションと神経の構造の解析を行った．その結果，正常皮膚では表皮神経はタイトジャンクションの内側にしか存在しないのに対して，アトピー性皮膚炎モデルにおいては，タイトジャンクションの形成異常が起こり，表皮神経がより外界に暴露されていることが示唆された．また，二光子レーザー顕微鏡を用いた皮膚感覚神経のCa2+イメージングを行った．その結果，皮膚炎が発症する直前から，異常なタイトジャンクションの近傍において感覚神経が活性化していることが示唆された．これらのことから，アトピー性皮膚炎の発症においては，表皮タイトジャンクションの異常により，表皮神経が外界からの刺激に長期間暴露されることによって，掻痒が引き起こされる可能性が考えられた．

    日本臨床免疫学会, 2017, 日本臨床免疫学会会誌, 40(4) (4), 269a - 269a, Japanese

  • Sakiyama, T, Umegaki-Arao, N, Sasaki, T, Kosaki, K, Amagai, M, Kubo, A
    Jan. 2017, J Dermatol, 44(1) (1), 102 - 103, English, International magazine

  • Kinoshita-Ise, M, Kubo, A, Sasaki, T, Umegaki-Arao, N, Amagai, M, Ohyama, M
    BACKGROUND: Autosomal recessive woolly hair/hypotrichosis (ARWH/H) is caused by mutations in LIPH. Homozygotes for the LIPH c.736T>A (p.C246S) mutation, the most prevalent genotype in Japanese patients, present varying degrees of hair loss; however, determinants of this phenotypic diversity remain elusive. OBJECTIVES: To establish methodologies for quantitative assessment of clinical severity and provide a detailed characterization to elucidate the factors contributing to phenotypic divergence. METHODS: Digital image analyses were conducted to convert clinical severities into numerical values. Eight patients with ARWH/H were classified into three groups (mild, severe, very severe), based on severity scores. Dermoscopic images were collected and assessed for total hair numbers and hair thickness for intergroup comparisons. RESULTS: The image analysis detected a difference in hair thickness but not in total hair numbers, between mild and severe cases. A marked decrease in total hair number was noted in an atypical very severe case. Histopathologically, a patient with a mild case demonstrated hair miniaturization and a high telogen/anagen ratio without a decrease in total hair count,
    Jan. 2017, Br J Dermatol, 176(1) (1), 138 - 144

  • M. Kinoshita-Ise, A. Kubo, T. Sasaki, N. Umegaki-Arao, M. Amagai, M. Ohyama
    Jan. 2017, BRITISH JOURNAL OF DERMATOLOGY, 176(1) (1), 138 - 144, English
    [Refereed]
    Scientific journal

  • Tomo Sakiyama, Noriko Umegaki-Arao, Takashi Sasaki, Kenjiro Kosaki, Masayuki Amagai, Akiharu Kubo
    Jan. 2017, JOURNAL OF DERMATOLOGY, 44(1) (1), 102 - 103, English
    [Refereed]

  • Miho Mukai, Keiji Tanese, Noriko Umegaki-Arao, Akiharu Kubo, Hayato Takahashi, Masayuki Amagai
    Nov. 2016, JOURNAL OF DERMATOLOGY, 43(11) (11), 1368 - 1370, English
    [Refereed]

  • Mariko Yokouchi, Toru Atsugi, Mark van Logtestijn, Reiko J. Tanaka, Mayumi Kajimura, Makoto Suematsu, Mikio Furuse, Masayuki Amagai, Akiharu Kubo
    Nov. 2016, ELIFE, 5(5) (5), e19593, English
    [Refereed]
    Scientific journal

  • 電子顕微鏡でランゲルハンス細胞はこうみえる!
    Akiharu Kubo
    Oct. 2016, Visual Dermatology, 15(11) (11), 1146 - 1147, Japanese

  • Akiharu Kubo
    Oct. 2016, Visual Dermatology, 15(11) (11), 1128 - 1129, Japanese

  • グリコール酸ピーリングにより皮膚症状が改善したFGFR3変異による全身性黒色表皮腫の母娘例および孤発例
    市山 進, 久保 亮治, 高山 良子, 又吉 武光, 川名 誠司, 佐伯 秀久, 船坂 陽子
    (一社)日本美容皮膚科学会, Aug. 2016, Aesthetic Dermatology, 26(2) (2), 267 - 267, Japanese

  • 田中 博子, 吉田 憲司, 根岸 亜津佐, 石井 健, 江藤 宏光, 佐々木 貴史, 久保 亮治, 石河 晃
    (株)協和企画, Aug. 2016, 皮膚病診療, 38(8) (8), 797 - 800, Japanese

  • Pseudoxanthoma elasticum-like papillary dermal elastolysisの1例と類縁疾患のダーモスコピー像の比較検討
    後藤あかね, 城光日, 久保亮治, 田中勝, 布袋祐子
    75歳,女性.初診の3年前より両側頸部・胸部・腋窩にそう痒を伴う黄白色の小丘疹が集簇多発してきた.精査にて眼病変,心血管病変の合併はなく.病理組織像では真皮乳頭層で弾性線維が減少している以外,特記すべき所見は認めなかった.以上よりpseudoxanthoma elasticum-like papillary dermal elastolysis(PXE-like PDE)と診断した.ダーモスコピーでは淡く境界不明瞭な黄白色の無構造領域が集簇・融合してみられた.臨床的にpseudoxanthoma elasticum(PDE)やwhite fibrous papulosis of the neck(WFPN)との鑑別が時に問題となる.PXE-like PDEのダーモスコピー像は,淡く境界不明瞭な黄白色の無構造領域である一方で,WFPNでは境界明瞭で均一な白色領域が存在する.PXEのダーモスコピーでは黄白色の無構造領域が粗大網状に融合し,健常部は淡紅色を呈する.(著者抄録)
    医学書院, Aug. 2016, 臨床皮膚科, 70(9) (9), 685 - 690, Japanese

  • Akiharu Kubo
    皮膚表皮には角質層とタイトジャンクション(TJ)の2つのバリアが存在する。ランゲルハンス細胞は表皮TJバリアの内側に通常は存在しているが、活性化するとTJバリアを越えて角質層直下まで樹状突起を延長し、TJバリアの外側で樹状突起の先端から抗原取得を行う。アトピー性皮膚炎の表皮では、表皮TJバリアを越えるランゲルハンス細胞が増加しており、表皮バリアの脆弱性により免疫応答が亢進している可能性がある。皮膚バリアをよい状態に保ち、外来抗原の侵入を抑えることにより、新たな経皮感作やIgEを介したアレルギー反応を予防できることが期待される。(著者抄録)
    Jun. 2016, MB Derma, 245, 8 - 14, Japanese

  • 皮膚バリアの破綻とアトピー性皮膚炎
    横内麻里子, 久保亮治, 天谷雅行
    Jun. 2016, Medical Science Digest, 42(6) (6), 22 - 25, Japanese

  • Akiharu Kubo
    CHILD(congenital hemidysplasia with ichthyosiform erythroderma and limb defects)症候群は,コレステロール生合成系の酵素をコードするNSDHLの機能欠失性変異による伴性優性遺伝性疾患である.NSDHLの活性低下により,コレステロール生合成系の反応が,NSDHLが司る反応の手前で止まってしまうことで,毒性を持った中間代謝物が蓄積し,皮膚症状を起こしていると考えられている.スタチンとコレステロールの外用により,コレステロール生合成系をNSDHLが介する反応よりも上流で堰き止める新しい治療法が考案され,CHILD症候群の皮疹の治療が初めて可能となった.(著者抄録)
    Apr. 2016, 臨床皮膚科, 70(5) (5), 53 - 56, Japanese

  • KID症候群の1例 感染コントロールの重要性
    角田梨沙, 大山学, 池田政身, 加藤りか, 戸田郁子, 坪田一男, 久保亮治
    26歳,女性.出生時より頭部無毛,耳介・爪甲の変形,掌蹠過角化,重度の感音性難聴を認めた.後に両眼角膜混濁をきたし,小児期より皮膚感染症・膿皮症を頻回に繰り返した.当院受診時,略全身の角化性紅斑,掌蹠のびまん性の潮紅と過角化,足底の牡蠣殻状角質付着,手指爪甲部に難治性潰瘍を認めた.GJB2がコードするコネキシン26にp.D50N変異を認め,KID症候群と診断した.直接鏡検でいずれの皮疹からも真菌要素が検出され,テルビナフィンの内服を開始し,体幹・四肢の角化性紅斑は略治した.角質肥厚の強い顔面・足底の皮疹はイトラコナゾールパルス療法により著明に改善した.手指の難治性潰瘍は感染コントロール後,切除/人工真皮移植で治癒した.本症では皮膚の易感染性を伴い,細菌・真菌感染症を繰り返す.その適切なコントロールが,患者QOLの改善および潰瘍・慢性炎症による皮膚癌発生の予防に寄与するのではないかと考えた.(著者抄録)
    医学書院, Apr. 2016, 臨床皮膚科, 70(4) (4), 347 - 352, Japanese

  • S. Ichiyama, Y. Funasaka, Y. Otsuka, R. Takayama, S. Kawana, H. Saeki, A. Kubo
    Mar. 2016, JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 30(3) (3), 442 - 445, English
    [Refereed]
    Scientific journal

  • Tomo Sakiyama, Akiharu Kubo
    Mar. 2016, JOURNAL OF DERMATOLOGY, 43(3) (3), 264 - 274, English

  • Yuki Hirota, Masato Sawada, Shih-Hui Huang, Takashi Ogino, Shinya Ohata, Akiharu Kubo, Kazunobu Sawamoto
    In many animal species, the production of new neurons (neurogenesis) occurs throughout life, in a specialized germinal region called the ventricular-subventricular zone (V-SVZ). In this region, neural stem cells undergo self-renewal and generate neural progenitor cells and new neurons. In the olfactory system, the new neurons migrate rostrally toward the olfactory bulb, where they differentiate into mature interneurons. V-SVZ-derived new neurons can also migrate toward sites of brain injury, where they contribute to neural regeneration. Recent studies indicate that two major branches of the Wnt signaling pathway, the Wnt/β-catenin and Wnt/planar cell polarity pathways, play essential roles in various facets of adult neurogenesis. Here, we review the Wnt signaling-mediated regulation of adult neurogenesis in the V-SVZ under physiological and pathological conditions.
    Feb. 2016, Neurochemical research, 41(1-2) (1-2), 222 - 30, English, International magazine
    [Refereed]

  • Jun Kikuchi, Yuko Kaneko, Hidenori Kasahara, Katsura Emoto, Akiharu Kubo, Shinichiro Okamoto, Tsutomu Takeuchi
    2016, INTERNAL MEDICINE, 55(12) (12), 1661 - 1665, English
    [Refereed]
    Scientific journal

  • Aiko Shiohama, Takashi Sasaki, Showbu Sato, Jun-ichi Sakabe, Taisuke Ito, Hideka Isoda, Yukari Zenke, Toshiaki Nakano, Tatsuo Maeda, Akira Ishiko, Kenji Kabashima, Yoshiki Tokura, Yoshihiko Mitsuhashi, Masayuki Amagai, Akiharu Kubo
    Jan. 2016, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 136(1) (1), 325 - 328, English
    [Refereed]

  • Takuji Masunaga, Masataka Saito, Takashi Sasaki, Akiharu Kubo, Masayuki Amagai, Akira Ishiko
    Dec. 2015, JOURNAL OF DERMATOLOGICAL SCIENCE, 80(3) (3), 220 - 223, English
    [Refereed]

  • 皮膚タイトジャンクションバリアとアトピー性皮膚炎
    久保 亮治
    Sep. 2015, アレルギーの臨床, 35(10) (10), 931 - 935, Japanese

  • 体表面バリアの進化と皮膚
    久保 亮治
    Aug. 2015, Visual Dermatology, 14(9) (9), 1022 - 1027, Japanese

  • 皮膚バリアとランゲルハンス細胞
    吉田和恵, 久保 亮治, 天谷雅行
    科学評論社, Jul. 2015, 臨床免疫・アレルギー科, 64(1) (1), 26 - 32, Japanese

  • Tomo Sakiyama, Akiharu Kubo, Takashi Sasaki, Taketo Yamada, Nobushige Yabe, Ken-ichi Matsumoto, Yuko Futei
    May 2015, JOURNAL OF DERMATOLOGY, 42(5) (5), 511 - 514, English
    [Refereed]
    Scientific journal

  • 小児皮膚疾患の遺伝カウンセリング
    久保 亮治
    May 2015, 皮膚科の臨床, 57(6) (6), 1044 - 1051, Japanese

  • CHILD症候群7例におけるコレステロール生合成経路阻害による治療効果と病態形成機構の検討
    久保 亮治, 梅垣 知子, 藤田 春美, 久保 亜紀子, 吉田 和恵, 森岡 眞治, 林 伸和, 臼田 俊和, 新関 寛徳, 高森 建二, 石河 晃, 末松 誠, 天谷 雅行
    (公社)日本皮膚科学会, Apr. 2015, 日本皮膚科学会雑誌, 125(4) (4), 918 - 918, Japanese

  • 経皮感作とアレルギー疾患
    吉田和恵, 久保 亮治
    Apr. 2015, Mebio, 32(4) (4), 16 - 22, Japanese

  • Kasai, H, Sasaki, T, Matsuzaki, H, Yoshioka, T, Nagao, K, Amagai, M, Ishiko, A, Kubo, A
    Mar. 2015, J Dermatol, 42(3) (3), 323 - 5, English, International magazine

  • Hiroko Kasai, Takashi Sasaki, Hitomi Matsuzaki, Toshiro Yoshioka, Keisuke Nagao, Masayuki Amagai, Akira Ishiko, Akiharu Kubo
    Mar. 2015, JOURNAL OF DERMATOLOGY, 42(3) (3), 323 - 325, English
    [Refereed]

  • 表皮バリア不全と経皮感作が招くアレルギー疾患
    久保 亮治, 天谷雅行
    Mar. 2015, 実験医学, 33(4) (4), 563 - 569, Japanese

  • 久保 亮治
    皮膚には角層のバリアと，その内側で液性環境の恒常性を保つタイトジャンクション（TJ）バリアの2つの物理的バリアが存在する．表皮内樹状細胞であるランゲルハンス細胞（LC）は，TJバリア外に樹状突起を延長して外来抗原を取得し，先制免疫の獲得に働くことを我々はマウスを用いて明らかにしてきた．本研究では，健康人皮膚と，角層バリア破綻が発症因子となるアトピー性皮膚炎（AD）患者皮膚の3次元観察を行った．ヒト皮膚でも活性化したLCはTJを突き抜けて樹状突起を角層直下へと延ばしていた．AD患者病変部では，活性化してTJ外に樹状突起を延ばしたLCが増加しており，経皮感作が亢進している可能性が示唆された．AD患者表皮には，inflammatory dendritic epidermal cell（IDEC）と呼ばれる，LCとは異なる特徴を持った樹状細胞が出現する．今回の観察により，IDECはLCと比較して表皮の深いところに位置し，周囲のLCが活性化してTJバリア外に樹状突起を延ばしている状況でも，常にTJバリア内に留まることを明らかにした．AD患者ではLCとIDECのいずれもがIgEレセプターを発現するが，TJ外に出た樹状突起先端に濃縮するlangerinとは異なり，IgEレセプターはTJバリアの内側の細胞膜に分布していた．すなわち，皮膚バリアを良い状態に保つことにより，新たな経皮感作やIgEを介したアレルギー反応を予防できることが予想され，AD患者の治療におけるスキンケアの重要性を示した．
    The Japan Society for Clinical Immunology, 2015, 日本臨床免疫学会会誌, 38(4) (4), 289b - 289b, Japanese

  • Mariko Yokouchi, Akiharu Kubo, Hiroshi Kawasaki, Kazue Yoshida, Ken Ishii, Mikio Furuse, Masayuki Amagai
    Jan. 2015, JOURNAL OF DERMATOLOGICAL SCIENCE, 77(1) (1), 28 - 36, English
    [Refereed]
    Scientific journal

  • 角層の形成機構と先天性角層バリア破綻疾患
    久保 亮治
    日本皮膚科学会, Dec. 2014, 日本皮膚科学会雑誌・臨時増刊号, 124(4) (4), 2672 - 2674, Japanese

  • 長島型掌蹠角化症
    久保 亮治
    Nov. 2014, 別冊 BIO Clinica：慢性炎症と疾患, 3(2) (2), 109 - 113, Japanese

  • Yoshida, K, Kubo, A, Fujita, H, Yokouchi, M, Ishii, K, Kawasaki, H, Nomura, T, Shimizu, H, Kouyama, K, Ebihara, T, Nagao, K, Amagai, M
    BACKGROUND: The stratum corneum and tight junctions (TJs) form physical barriers in the epidermis. Dendrites of activated Langerhans cells (LCs) extend beyond the TJs to capture external antigens in mice. LCs and inflammatory dendritic epidermal cells (IDECs) are observed in the skin of patients with atopic dermatitis (AD). OBJECTIVE: We sought to investigate the characteristics of LCs and IDECs and the distribution of their antigen capture receptors in relation to TJs in normal and AD skin. METHODS: We characterized the interactions of LCs and IDECs with TJs and the expression patterns of langerin and FcepsilonRI by using whole-mount epidermal sheets from healthy subjects and patients with AD, ichthyosis vulgaris, and psoriasis vulgaris. RESULTS: As in mouse skin, activated LCs penetrate TJs in human skin. The number of LCs with TJ penetration increased approximately 5-fold in erythematous lesional skin of patients with AD but not in nonlesional skin of patients with AD or lesions of patients with ichthyosis vulgaris or psoriasis. In contrast, IDECs localized in the lower part of the epidermis, and their dendrites extended horizontally without penetration through TJs. Although lan
    Oct. 2014, J Allergy Clin Immunol, 134(4) (4), 856 - 64, English, International magazine
    [Refereed]
    Scientific journal

  • Kazue Yoshida, Akiharu Kubo, Harumi Fujita, Mariko Yokouchi, Ken Ishii, Hiroshi Kawasaki, Toshifumi Nomura, Hiroshi Shimizu, Keisuke Kouyama, Tamotsu Ebihara, Keisuke Nagao, Masayuki Amagai
    Oct. 2014, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 134(4) (4), 856 - 864, English
    [Refereed]
    Scientific journal

  • 単純ヘルペスウイルスの再活性化による口腔内・食道潰瘍を呈した薬剤性過敏症症候群の1例
    森本亜里, 舩越建, 福島彩乃, 久保亮治, 海老原全, 林田哲, 真杉洋平, 亀山香織, 永尾圭介
    医学書院, Oct. 2014, 臨床皮膚科, 68(11) (11), 873 - 878, Japanese

  • Jun-ichi Sakabe, Rieko Kabashima-Kubo, Akiharu Kubo, Takashi Sasaki, Yoshiki Tokura
    Aug. 2014, JOURNAL OF DERMATOLOGY, 41(8) (8), 764 - 765, English
    [Refereed]
    Scientific journal

  • 長島型掌蹠角化症 遺伝子解析も含めて
    仁木真理子, 広瀬憲志, 塩濱愛子, 久保亮治
    Aug. 2014, 皮膚病診療, 36(8) (8), 749 - 752, Japanese

  • 皮膚バリア構造・機能のイメージング手法
    久保 亮治
    Jul. 2014, 感染・炎症・免疫, 44(2) (2), 120 - 130, Japanese

  • 皮膚バリアとタイトジャンクション
    久保 亮治
    Jul. 2014, 炎症と免疫, 22(4) (4), 12 - 23, Japanese

  • 長島型掌蹠角化症ものがたり 疾患概念の確立から、原因遺伝子SERPINB7の同定にいたるまで
    久保 亮治
    Jun. 2014, 皮膚病診療, 36(6) (6), 486 - 493, Japanese

  • 皮膚表皮が持つバリア構造と機能からみたアレルギー疾患治療戦略
    久保 亮治
    May 2014, 薬学雑誌, 134(2) (2), 623 - 627, Japanese

  • Kubo, Akiharu
    2014, Journal of Investigative Dermatology, 134(8) (8)
    Scientific journal

  • Akiharu Kubo, Aiko Shiohama, Takashi Sasaki, Kazuhiko Nakabayashi, Hiroshi Kawasaki, Toru Atsugi, Showbu Sato, Atsushi Shimizu, Shuji Mikami, Hideaki Tanizaki, Masaki Uchiyama, Tatsuo Maeda, Taisuke Ito, Jun-ichi Sakabe, Toshio Heike, Torayuki Okuyama, Rika Kosaki, Kenjiro Kosaki, Jun Kudoh, Kenichiro Hata, Akihiro Umezawa, Yoshiki Tokura, Akira Ishiko, Hironori Niizeki, Kenji Kabashima, Yoshihiko Mitsuhashi, Masayuki Amagai
    Nov. 2013, AMERICAN JOURNAL OF HUMAN GENETICS, 93(5) (5), 945 - 956, English
    [Refereed]
    Scientific journal

  • Takashi Sasaki, Aiko Shiohama, Akiharu Kubo, Hiroshi Kawasaki, Akemi Ishida-Yamamoto, Taketo Yamada, Takayuki Hachiya, Atsushi Shimizu, Hideyuki Okano, Jun Kudoh, Masayuki Amagai
    Nov. 2013, Journal of Allergy and Clinical Immunology, 132(5) (5), 1111 - e4, English
    [Refereed]
    Scientific journal

  • Kazue Yoshida, Mariko Yokouchi, Keisuke Nagao, Ken Ishii, Masayuki Amagai, Akiharu Kubo
    Aug. 2013, JOURNAL OF DERMATOLOGICAL SCIENCE, 71(2) (2), 89 - 99, English
    [Refereed]
    Scientific journal

  • Akiharu Kubo, Yuiko Oura, Takashige Hirano, Yumi Aoyama, Showbu Sato, Kaori Nakamura, Yujiro Takae, Masayuki Amagai
    Jul. 2013, Journal of Dermatology, 40(7) (7), 553 - 557, English
    [Refereed]
    Scientific journal

  • 丘疹性ムチン沈着症の1例
    森下 加奈子, 福田 桂太郎, 久保 亮治, 海老原 全, 高江 雄二郎
    (公社)日本皮膚科学会, Mar. 2013, 日本皮膚科学会雑誌, 123(3) (3), 318 - 318, Japanese

  • Akiharu Kubo, Keisuke Nagao, Masayuki Amagai
    Humana Press Inc., 2013, Methods in Molecular Biology, 961, 119 - 127, English
    [Refereed]
    Scientific journal

  • Akiharu Kubo, Itsuko Ishizaki, Akiko Kubo, Hiroshi Kawasaki, Keisuke Nagao, Yoshiharu Ohashi, Masayuki Amagai
    2013, Scientific Reports, 3, 1731, English
    [Refereed]
    Scientific journal

  • 乳癌の放射線治療部位に生じた限局性水疱性類天疱瘡の１例
    松崎ひとみ, 山上淳, 久保亮治, 永尾圭介, 大山学, 海老原全, 天谷雅行
    医学書院, Sep. 2012, 臨床皮膚科, 66(19) (19), 757 - 760, Japanese
    Scientific journal

  • Keisuke Nagao, Tetsuro Kobayashi, Kazuyo Moro, Manabu Ohyama, Takeya Adachi, Daniela Y. Kitashima, Satoshi Ueha, Keisuke Horiuchi, Hideaki Tanizaki, Kenji Kabashima, Akiharu Kubo, Young-hun Cho, Bjorn E. Clausen, Kouji Matsushima, Makoto Suematsu, Glaucia C. Furtado, Sergio A. Lira, Joshua M. Farber, Mark C. Udey, Masayuki Amagai
    Aug. 2012, NATURE IMMUNOLOGY, 13(8) (8), 744 - +, English
    [Refereed]
    Scientific journal

  • Hiroshi Kawasaki, Keisuke Nagao, Akiharu Kubo, Tsuyoshi Hata, Atsushi Shimizu, Hideaki Mizuno, Taketo Yamada, Masayuki Amagai
    Jun. 2012, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 129(6) (6), 1538 - +, English
    [Refereed]
    Scientific journal

  • Aileen Sandilands, Sara J. Brown, Christabelle S. Goh, Elizabeth Pohler, Neil J. Wilson, Linda E. Campbell, Kenichi Miyamoto, Akiharu Kubo, Alan D. Irvine, Fatema Thawer-Esmail, Colin S. Munro, W. H. Irwin McLean, Jun Kudoh, Masayuki Amagai, Takeshi Matsui
    May 2012, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 132(5) (5), 1507 - 1510, English
    [Refereed]
    Scientific journal

  • 長期にわたり経過を観察し得た劣性栄養障害型先天性表皮水疱症の1例
    久保 亮治, 永尾 圭介, 天谷 雅行, 花房 崇明, 玉井 克人, 橋本 公二
    日本皮膚科学会-西部支部, Apr. 2012, 西日本皮膚科, 74(2) (2), 211 - 211, Japanese

  • Akiharu Kubo, Keisuke Nagao, Masayuki Amagai
    Feb. 2012, JOURNAL OF CLINICAL INVESTIGATION, 122(2) (2), 440 - 447, English
    [Refereed][Invited]
    Scientific journal

  • 川崎 洋, 永尾 圭介, 久保 亮治, 畑 毅, 清水 篤, 水野 秀昭, 山田 健人, 天谷 雅行
    フィラグリンの遺伝子変異は，アトピー性皮膚炎の主要な発症因子として報告されている．私たちは本研究で，フィラグリン欠損（Flg−/−）マウスを作成し，角層のバリア機能維持及び経皮免疫応答におけるフィラグリンの影響について検討した．
      生後早期のFlg−/−マウスは，落屑を伴い乾皮症様の外観を呈した．フィラグリンの分解産物を主な構成成分とするNMF（Natural moisturizing factor）はFlg−/−角層で著しい減少を認めたものの，角層内水分量や経皮水分蒸散量は正常だった．テープストリップを用いた実験から，物理刺激によるFlg−/−皮膚での角層剥離の亢進が示された．電子顕微鏡による観察から，Flg−/−角層におけるケラチンパターンの消失が確認され，これがFlg−/−角層の脆弱性に関与している可能性が示唆された．続いてカルセイン含有リポソームをマウス皮膚に塗布し，共焦点レーザー顕微鏡で観察したところ，Flg−/−角層で色素透過性の亢進を認めた．これらFlg−/−角層の機能異常は，ハプテン誘導性接触過敏反応やタンパク抗原経皮塗布後の液性免疫応答の亢進をもたらした．
      我々が作成したFlg−/−マウスは，in vivoでのフィラグリンの機能を正しく評価し，バリア機能異常を有する皮膚への経皮的抗原曝露から疾患が発症するまでのアトピー性皮膚炎発症機序の解明につながる有用なツールとなる．
    The Japan Society for Clinical Immunology, 2012, 日本臨床免疫学会会誌, 35(4) (4), 321a - 321a, Japanese

  • Anna De Benedetto, Akiharu Kubo, Lisa A. Beck
    Nature Publishing Group, 2012, Journal of Investigative Dermatology, 132(3) (3), 949 - 963, English
    [Refereed][Invited]
    Scientific journal

  • 粘膜/皮膚免疫 医学応用の視点より タイトジャンクションを介したランゲルハンス細胞の抗原獲得は実験的ブドウ球菌性熱傷様皮膚症候群において先制的な液性免疫を担う(Langerhans cells confer pre-emptive immunity via antigen capture through tight junctions in experimental staphylococcal scalded skin syndrome)
    永尾 圭介, 大内 健嗣, 久保 亮治, 藤猪 英樹, 小安 重夫, 天谷 雅行
    (NPO)日本免疫学会, Nov. 2011, 日本免疫学会総会・学術集会記録, 40, 184 - 184, English

  • Takeshi Matsui, Kenichi Miyamoto, Akiharu Kubo, Hiroshi Kawasaki, Tamotsu Ebihara, Kazuya Hata, Shinya Tanahashi, Shizuko Ichinose, Issei Imoto, Johji Inazawa, Jun Kudoh, Masayuki Amagai
    Jun. 2011, EMBO MOLECULAR MEDICINE, 3(6) (6), 320 - 333, English
    [Refereed]
    Scientific journal

  • Kawasaki, H. Kubo, A. Sasaki, T. Amagai, M
    May 2011, Curr Probl Dermatol, 41, 35-46, English
    [Refereed]
    Scientific journal

  • KUBO Akiharu
    Skin is the structure that covers our body and protects it from not only the entry of pathogens or allergens but also from the leakage of water, solutes or nutrients. These outside-in and inside-out skin barrier functions are dependent on the epidermis, a stratified epithelial cellular sheet. While mucus covers the epidermis in fish and amphibian tadpoles, terminally differentiated cornified cellular sheets called stratum corneum (SC) constitute the outermost epidermal barrier in amphibian adults, reptiles, birds and mammals. Beneath the mucus or SC, apical paracellular spaces of epidermal cells are sealed with tight junctions (TJs) that might limit paracellular leakage of water and electrolytes to maintain fluid homeostasis. We have recently reported in mice that Langerhans cells (LCs) elongate their dendrites to penetrate through epidermal TJs upon activation and uptake antigens from extra-TJ environment. During antigen uptake, new TJs are formed between keratinocytes and LC dendrites to maintain the integrity of epidermal TJ barriers. To understand the epidermal barrier system and its deficiency observed in human skin diseases, we need to re-evaluate human epidermal barrier as a composite barrier consisting of SC and TJs and to investigate the molecular mechanism and immunological consequences of the extra-TJ antigen uptake activity of LCs.
    The Japan Society for Clinical Immunology, Apr. 2011, Jpn. J. Clin. Immunol., 34(2) (2), 76 - 84, Japanese

  • KUBO Akiharu
    Skin is the structure that covers our body and protects it not only from the entry of pathogens or allergens but also from the leakage of water, solutes or nutrients. These outside-in and inside-out skin barrier functions are dependent on the epidermis, a stratified epithelial cellular sheet. Terminally differentiated cornified cellular sheets called stratum corneum (SC) constitute the outermost epidermal barrier. Beneath the SC, apical paracellular spaces of epidermal cells are sealed with tight junctions (TJs). We have recently reported in mice that Langerhans cells (LCs) elongate their dendrites to penetrate through epidermal TJs upon activation and uptake antigens from extra-TJ environment. To understand the epidermal barrier system and its deficiency observed in human skin diseases, especially in atopic dermatitis, we need to re-evaluate human epidermal barrier as a composite barrier consisting of SC and TJs and to investigate the molecular mechanism and immunological consequences of the extra-TJ antigen uptake activity of LCs.Skin Research, Suppl. 16: 5-10, 2011
    Meeting of Osaka Dermatological Association/Meeting of Keiji Dermatological Association, 2011, Hifu no kagaku, 10(16) (16), 5 - 10, Japanese

  • Takeshi Ouchi, Akiharu Kubo, Mariko Yokouchi, Takeya Adachi, Tetsuro Kobayashi, Daniela Y. Kitashima, Hideki Fujii, Björn E. Clausen, Shigeo Koyasu, Masayuki Amagai, Keisuke Nagao
    Rockefeller University Press, 2011, The Journal of Experimental Medicine, 208(13) (13), 2607 - 2613, English
    [Refereed]
    Scientific journal

  • ランゲルハンス細胞による抗原の補捉機序
    久保亮治, 天谷雅行
    科学評論社, Dec. 2010, 臨床免疫・アレルギー科, 54(6) (6), 701-709 - 709, Japanese
    Scientific journal

  • 特別講演：未来皮膚科学：Molecular Barriology of the Skin
    Kubo Akiharu
    Nov. 2010, 日本皮膚科学会雑誌, 120(13) (13), 2521-2523, Japanese
    Scientific journal

  • 手術瘢痕部位に初発した落葉状天疱瘡の1例
    綿貫沙織, 石橋正史, 山本享子, 久保亮治, 陳科榮
    医学書院, Oct. 2010, 臨床皮膚科, 64(11) (11), 835-839 - 839, Japanese
    Scientific journal

  • ランゲルハンス細胞による外来抗原捕捉機構
    久保亮治, 天谷雅行
    Oct. 2010, 感染・炎症・免疫, 40(3) (3), 267-270, Japanese
    Scientific journal

  • 特異な臨床を呈した環状肉芽腫の1例
    河野 通良, 佐藤 友隆, 久保 亮治, 石河 晃
    (公社)日本皮膚科学会, Sep. 2010, 日本皮膚科学会雑誌, 120(10) (10), 2073 - 2073, Japanese
    [Refereed]

  • 松本悠子, 吉田和恵, 久保亮治, 石井健, 天谷雅行, 石河晃
    (株)医学書院, Jun. 2010, 臨床皮膚科, 64(7) (7), 464-467 - 467, Japanese
    Scientific journal

  • Catharina Sagita Moniaga, Gyohei Egawa, Hiroshi Kawasaki, Mariko Hara-Chikuma, Tetsuya Honda, Hideaki Tanizaki, Saeko Nakajima, Atsushi Otsuka, Hiroyuki Matsuoka, Akiharu Kubo, Jun-ichi Sakabe, Yoshiki Tokura, Yoshiki Miyachi, Masayuki Amagai, Kenji Kabashima
    May 2010, AMERICAN JOURNAL OF PATHOLOGY, 176(5) (5), 2385 - 2393, English
    [Refereed]
    Scientific journal

  • 久保 亮治
    一般社団法人 日本アレルギー学会, 2010, アレルギー, 59(9) (9), 1247 - 1247, Japanese

  • Akiharu Kubo, Keisuke Nagao, Mariko Yokouchi, Hiroyuki Sasaki, Masayuki Amagai
    Dec. 2009, JOURNAL OF EXPERIMENTAL MEDICINE, 206(13) (13), 2937 - 2946, English
    Scientific journal

  • 抗デスモグレイン1抗体陽性IgG/IgA 天疱瘡の1例
    星野洋良, 林裕嘉, 森布衣子, 木花いづみ, 久保亮治, 石井健, 天谷雅行
    医学書院, Nov. 2009, 臨床皮膚科, 63(12) (12), 927-931 - 931, Japanese
    Scientific journal

  • Keiji Tanese, Akane Akiyoshi, Masataka Saito, Akiharu Kubo, Masaki Takanashi, Akira Ishiko
    Jul. 2009, JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 61(1) (1), 167 - 169, English
    Scientific journal

  • A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming
    Fallon, P. G.Sasaki, T.Sandilands, A.Campbell, L. E.Saunders, S. P.Mangan, N. E.Callanan, J. J.Kawasaki, H.Shiohama, A.Kubo, A.Sundberg, J.P.Presland, R. B.Fleckman, P.Shimizu, N.Kudoh, J.Irvine, A. D.Amagai, M.McLean, W H I
    Apr. 2009, Nat Genet, 41, 602-608 - 608, English
    Scientific journal

  • Akiharu Kubo, Akiko Yuba-Kubo, Sachiko Tsukita, Shoichiro Tsukita, Masayuki Amagai
    Dec. 2008, MOLECULAR BIOLOGY OF THE CELL, 19(12) (12), 5338 - 5346, English
    Scientific journal

  • Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4 - A candidate for psychiatric illnesses
    Atsushi Kamiya, Perciliz L. Tan, Ken-ichiro Kubo, Caitlin Engelhard, Koko Ishizuka, Akiharu Kubo, Sachiko Tsukita, Ann E. Pulver, Kazunori Nakajima, Nicola G. Cascella, Nicholas Katsanis, Akira Sawa
    Sep. 2008, ARCHIVES OF GENERAL PSYCHIATRY, 65(9) (9), 996 - 1006, English
    Scientific journal

  • Junko Yamane, Akiharu Kubo, Kazuhisa Nakayama, Akiko Yuba-Kubo, Tatsuya Katsuno, Shoichiro Tsukita, Sachiko Tsukita
    Oct. 2007, EXPERIMENTAL CELL RESEARCH, 313(16) (16), 3472 - 3485, English
    Scientific journal

  • Gene knockout analysis of two gamma-tubulin isoforms in mice.
    Akiko Yuba-Kubo, Akiharu Kubo, Masaki Hata, Shoichiro Tsukita
    Gamma-tubulin regulates the nucleation of microtubules, but knowledge of its functions in vivo is still fragmentary. Here, we report the identification of two closely related gamma-tubulin isoforms, TUBG1 and TUBG2, in mice, and the generation of TUBG1- and TUBG2-deficient mice. TUBG1 was expressed ubiquitously, whereas TUBG2 was primarily detected in the brain. The development of TUBG1-deficient (Tubg1-/-) embryos stopped at the morula/blastocyst stages due to a characteristic mitotic arrest: the mitotic spindle was highly disorganized, and disorganized spindles showed one or two pole-like foci of bundled MTs that were surrounded by condensed chromosomes. TUBG2 was expressed in blastocysts, but could not rescue the TUBG1 deficiency. By contrast, TUBG2-deficient (Tubg2-/-) mice were born, grew, and intercrossed normally. In the brain of wild-type mice, TUBG2 was expressed in approximately the same amount as TUBG1, but no histological abnormalities were found in the Tubg2-/- brain. These findings indicated that TUBG1 and TUBG2 are not functionally equivalent in vivo, that TUBG1 corresponds to conventional gamma-tubulin, and that TUBG2 may have some unidentified function in the brain.
    Jun. 2005, Developmental biology, 282(2) (2), 361 - 73, English, International magazine
    Scientific journal

  • H Ishikawa, A Kubo, S Tsukita, S Tsukita
    May 2005, NATURE CELL BIOLOGY, 7(5) (5), 517 - U79, English
    [Refereed]
    Scientific journal

  • M Matsuda, A Kubo, M Furuse, S Tsukita
    Mar. 2004, JOURNAL OF CELL SCIENCE, 117(7) (7), 1247 - 1257, English
    Scientific journal

  • 培養上皮細胞におけるGFP-claudinの細胞内への取り込み機構のライブ観察
    松田 美穂, 久保 亮治, 古瀬 幹夫, 月田 承一郎
    (一社)日本細胞生物学会, May 2003, 日本細胞生物学会大会講演要旨集, 56回, 33 - 33, Japanese

  • Non-membranous granular organelle consisting of PCM-1: subcellular distribution and cell-cycledependent assembly/disassembly
    A Kubo, S Tsukita
    Mar. 2003, JOURNAL OF CELL SCIENCE, 116(5) (5), 919 - 928, English
    [Refereed]
    Scientific journal

  • M Furuse, M Hata, K Furuse, Y Yoshida, A Haratake, Y Sugitani, T Noda, A Kubo, S Tsukita
    Mar. 2002, JOURNAL OF CELL BIOLOGY, 156(6) (6), 1099 - 1111, English
    [Refereed]
    Scientific journal

  • Centriolar satellites: Molecular characterization, ATP-dependent movement toward centrioles and possible involvement in ciliogenesis
    A Kubo, H Sasaki, A Yuba-Kubo, S Tsukita, N Shiina
    Nov. 1999, JOURNAL OF CELL BIOLOGY, 147(5) (5), 969 - 979, English
    [Refereed]
    Scientific journal

  • Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen (desmoglein 3)
    A Kubo, M Amagai, T Hashimoto, T Doi, M Higashiyama, K Hashimoto, K Yoshikawa
    Jul. 1997, BRITISH JOURNAL OF DERMATOLOGY, 137(1) (1), 109 - 113, English
    [Refereed]
    Scientific journal

  • Epidermolysis bullosa acquisita exacerbated by systemic estrogen and progesterone treatment and pregnancy
    A Kubo, K Hashimoto, C Inoue, T Hashimoto, K Yoshikawa
    May 1997, JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 36(5) (5), 792 - 794, English
    [Refereed]
    Scientific journal

  • HISTAMINE-INDUCED CYCLIC-AMP ACCUMULATION IN TYPE-1 AND TYPE-2 ASTROCYTES IN PRIMARY CULTURE
    A KUBO, H FUKUI, N INAGAKI, A KANAMURA, H WADA
    Nov. 1991, EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 208(3) (3), 249 - 253, English
    [Refereed]
    Scientific journal

  • Fukui, H., Inagaki, N., Ito, S., Kubo, A., Kondoh, H., Yamatodani, A., Wada, H.
    1991, Agents and Actions, 33(SUPPL.) (SUPPL.)
    Scientific journal

  • Kiyokawa, H., Fukui, H., Mizuguchi, H., Kubo, A., Kono, N., Tarui, S., Wada, H.
    1991, Journal of Biochemistry, 110(1) (1)
    Scientific journal

  • ADENOSINE INDUCES SYSTEM-A AMINO-ACID-TRANSPORT IN CULTURED RAT HEPATOCYTES
    KIYOKAWA, H., FUKUI, H., MIZUGUCHI, H., KUBO, A., KONO, N., TARUI, S., WADA, H.
    1991, Journal of Biochemistry, 110(1) (1)
    Scientific journal

■ MISC
  • 尿路感染に伴う急性汎発性膿疱性細菌疹と考えた1例
    南 裕介, 織田 好子, 福永 淳, 久保 亮治, 岡野 光真, 坂口 一彦
    日本皮膚科学会-大阪地方会・京滋地方会, Dec. 2022, 皮膚の科学, 21(4) (4), 351 - 351, Japanese

  • 尿路感染に伴う急性汎発性膿疱性細菌疹と考えた1例
    南 裕介, 織田 好子, 福永 淳, 久保 亮治, 岡野 光真, 坂口 一彦
    日本皮膚科学会-大阪地方会・京滋地方会, Dec. 2022, 皮膚の科学, 21(4) (4), 351 - 351, Japanese

  • 蕁麻疹診療における問診票を用いたスクリーニングの有用性の検討 問診票を用いてどこまで蕁麻疹の病型を絞り込めるか
    坪井 美樹, 今村 真也, 鷲尾 健, 川村 真実, 福本 毅, 織田 好子, 水野 真由子, 久保 亮治, 福永 淳
    (一社)日本皮膚免疫アレルギー学会, Dec. 2022, 日本皮膚免疫アレルギー学会総会学術大会プログラム・抄録集, 52回, 179 - 179, Japanese

  • 熊谷 淳, 松澤 惇, 今村 真也, 織田 好子, 福本 毅, 福永 淳, 久保 亮治
    (一社)日本アレルギー学会, Aug. 2022, アレルギー, 71(6-7) (6-7), 824 - 824, Japanese

  • 卵黄による食物依存性運動誘発アナフィラキシーの1例
    川村 真実, 織田 好子, 田中 彰浩, 山田 はるひ, 福永 淳, 久保 亮治, 木谷 美湖野
    日本皮膚科学会-大阪地方会・京滋地方会, Mar. 2022, 皮膚の科学, 21(1) (1), 63 - 64, Japanese

  • 柴田 慶子, 国定 充, 錦織 千佳子, 久保 亮治, 宮井 俊輔, 倉橋 浩樹, 河盛 重紀
    (株)協和企画, Mar. 2022, 皮膚病診療, 44(3) (3), 236 - 239, Japanese

  • 炭酸ガスレーザーが有効であったCYLD変異による多発性家族性毛包上皮腫の1例
    齋藤苑子, 小野紀子, 大内健嗣, 青木里美, 佐々木貴史, 勝野正子, 天谷雅行, 久保亮治, 久保亮治
    2022, 皮膚かたち研究学会学術大会プログラム・抄録集, 48th

  • Hyperkeratosis lenticularis perstans(Flegel病)と考えた1例
    角田美鈴, 角田梨沙, 齋藤苑子, 小野紀子, 平井郁子, 舩越建, 久保亮治, 三井純雪
    2022, 日本皮膚科学会雑誌, 132(10) (10)

  • 腋窩・臍・鼠径部に島状の正常皮膚を認めたCARD14変異による乾癬/PRPV型の1例
    齋藤苑子, 田中諒, 青木里美, 天谷雅行, 久保亮治, 新関寛徳
    2021, 日本皮膚科学会雑誌, 131(6) (6)

  • Y. Inoue-Masuda, I. Hirai, E. Yanagisawa, Y. Kurihara, T. Funakoshi, J. Yamagami, M. Amagai, A. Kubo
    Blackwell Publishing Ltd, 01 Aug. 2020, Journal of the European Academy of Dermatology and Venereology, 34(8) (8), e388 - e391, English
    Report scientific journal

  • N. Umegaki-Arao, N. Ono, R. Tanaka, T. Sasaki, H. Fujita, A. Shiohama, S. Aoki, M. Amagai, A. Kubo
    Blackwell Publishing Ltd, 01 May 2020, British Journal of Dermatology, 182(5) (5), 1303 - 1305, English
    Report scientific journal

  • 18番染色体長腕の片親性ダイソミーによりSERPINB7 c.796C>T変異がホモ接合となって発症した長島型掌蹠角化症の1例
    早川 道太郎, 田原 海, 小野 紀子, 青木 里美, 天谷 雅行, 久保 亮治, 河合 智子, 中林 一彦
    (公社)日本皮膚科学会, Mar. 2020, 日本皮膚科学会雑誌, 130(3) (3), 410 - 410, Japanese

  • 22番染色体長腕の部分欠失により小顎症・二分口蓋垂・神経線維腫症II型を合併した1例
    齋藤苑子, 小野紀子, 青木里美, 佐々木貴史, 小崎健次郎, 久世文也, 中林一彦, 天谷雅行, 久保亮治
    2020, 日本皮膚科学会雑誌, 130(5) (5)

  • 皮膚バリアの構造と機能のイメージング解析
    久保亮治
    Jan. 2020, Precision Medicine, 3(1) (1), 1 - 4, Japanese

  • 皮膚バリア機能と経皮感作
    横内麻里子, 久保亮治
    Oct. 2019, OCULISTA, 79, 7 - 13, Japanese

  • Mao Satake, Kyoko Kudo, Takashi Sasaki, Masutaka Furue, Akiharu Kubo
    Journal of Dermatology, Aug. 2019, The Journal of Dermatology, 46(8) (8), e296 - e298, English
    [Refereed]

  • 皮脂欠乏性湿疹・貨幣状湿疹
    久保亮治, 小野紀子
    Jul. 2019, 日本医事新報, 4967, 47, Japanese

  • 皮膚バリア機能
    吉田和恵, 久保亮治
    May 2019, 皮膚科の臨床（増刊号）, 61(6) (6), 721 - 731, Japanese

  • 天疱瘡の寛解後に水疱性類天疱瘡を発症した1例
    田原海, 古市祐樹, 新川宏樹, 齋藤昌孝, 久保亮治, 天谷雅行, 舩越建, 山上淳
    (公社)日本皮膚科学会, May 2019, 第883回日本皮膚科学会東京地方会（城西地区）, 129(6) (6), 1348 - 1348, Japanese

  • Chediak-Higashi症候群の1例
    福地 健祐, 龍野 一樹, 戸倉 新樹, 坂口 公祥, 佐野 伸一朗, 久保 亮治
    (公社)日本皮膚科学会, Apr. 2019, 日本皮膚科学会雑誌, 129(4) (4), 594 - 594, Japanese

  • Yoshida K, Sadamoto M, Sasaki T, Kubo A, Ishiko A
    Journal of Dermatology, Feb. 2019, Journal of Dermatology, 46(2) (2), e61 - e63, English, International magazine

  • NCSTN変異を同定したfamilial acne inversaの姉妹例
    小野 紀子, 田中 諒, 天谷 雅行, 久保 亮治, 鈴木 寿人, 小崎 健次郎, 中林 一彦, 秦 健一郎
    (公社)日本皮膚科学会, Nov. 2018, 日本皮膚科学会雑誌, 128(12) (12), 2672 - 2672, Japanese
    [Refereed]

  • Tanaka, R. Umegaki-Arao, N. Sasaki, T. Aoki, S. Yoshida, K. Niizeki, Kubo, A
    Journal of Dermatology, Nov. 2018, J Dermatol, 45(11) (11), e302 - e303, English
    [Refereed]

  • Nomura H, Kurihara Y, Saito M, Fukushima A, Shintani Y, Shiiyama R, Toshima S, Kamata A, Yamagami J, Funakoshi T, Kameyama K, Amagai M, Kubo A, Umegaki-Arao N
    Journal of the European Academy of Dermatology and Venereology, Oct. 2018, J Eur Acad Dermatol Venereol, 32(10) (10), e386 - e389
    [Refereed]

  • 関節可動域の経時的な測定で病勢を評価しえた好酸球性筋膜炎の1例
    朝比奈泰彦, 新川宏樹, 齋藤苑子, 田中諒, 舩越建, 久保亮治
    (公社)日本皮膚科学会, Aug. 2018, 第879回日本皮膚科学会東京地方会（城西地区）, 128(9) (9), 1962 - 1963, Japanese

  • 再発性陰部ヘルペスを契機に診断し得た選択的IgM欠損症の1例
    鎌田亜紀, 田中諒, 舩越建, 久保亮治, 天谷雅行, 谷川瑛子
    (公社)日本皮膚科学会, Aug. 2018, 第879回日本皮膚科学会東京地方会（城西地区）, 128(9) (9), 1961 - 1961, Japanese

  • Yokouchi M, Kubo A
    © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd The skin forms a life-sustaining barrier between the organism and the physical environment. The physical barrier of the skin is mainly comprised of the stratum corneum (SC) and tight junctions (TJs). In recent years, there have been significant advances in our understanding of the epidermal TJ function, composition and regulation. In contrast to the SC, TJs are highly dynamic structures. It was discovered that spatiotemporal regulation of dynamic TJ replacement from cell to cell maintains the TJ barrier homeostasis of the skin, despite continuous cellular turnover. This review summarizes current knowledge about how TJ barrier homeostasis is maintained in simple and stratified epithelia, and how diseases and other conditions affect the TJ barrier in the skin.
    Experimental Dermatology, Aug. 2018, Exp Dermatol, 27(8) (8), 876 - 883, English

  • 鼻翼部と内眼角に皮膚潰瘍を生じ治療に難渋した慢性肉芽腫症の1例
    増田容子, 平井郁子, 柳澤絵里加, 栗原佑一, 舩越建, 山上淳, 櫻岡浩一, 天谷雅行, 久保亮治
    (公社)日本皮膚科学会, Jul. 2018, 第878回日本皮膚科学会東京地方会（城西地区）, 128(8) (8), 1669 - 1669, Japanese

  • 小児の遺伝性疾患
    久保亮治
    Jun. 2018, MB Derma, 271, 72 - 82, Japanese

  • H. Horikawa, Y. Kurihara, T. Funakoshi, N. Umegaki-Arao, H. Takahashi, A. Kubo, A. Tanikawa, N. Kodani, Y. Minami, S. Meguro, H. Itoh, K. Izumi, W. Nishie, H. Shimizu, M. Amagai, J. Yamagami
    Blackwell Publishing Ltd, 01 Jun. 2018, British Journal of Dermatology, 178(6) (6), 1462 - 1463, English
    Report scientific journal

  • Aiko Yamauchi, Akiharu Kubo, Noriko Ono, Aiko Shiohama, Daisuke Tsuruta, Kazuyoshi Fukai
    Blackwell Publishing Ltd, 01 May 2018, Journal of Dermatology, 45(5) (5), e112 - e113, English
    Report scientific journal

  • 皮膚の微細構造"ケルビン14面体モデル"
    横内麻里子, 久保亮治
    Apr. 2018, 臨床皮膚科（増刊号）, 72(5) (5), 38 - 44, Japanese

  • Yoshie Fukunaga, Akiharu Kubo, Takashi Sasaki, Daisuke Tsuruta, Kazuyoshi Fukai
    Blackwell Publishing Ltd, 01 Apr. 2018, Journal of Dermatology, 45(4) (4), e72 - e73, English
    Report scientific journal

  • Miho Mukai, Harumi Fujita, Noriko Umegaki-Arao, Takashi Sasaki, Fumiyo Yasuda-Sekiguchi, Tsuyoshi Isojima, Sachiko Kitanaka, Masayuki Amagai, Akiharu Kubo
    Elsevier Ireland Ltd, 01 Apr. 2018, Journal of Dermatological Science, 90(1) (1), 90 - 93, English
    Report scientific journal

  • アザチオプリンで汎血球減少、脱毛を生じNUDT15変異を認めた尋常性天疱瘡の1例
    鎌田 亜紀, 福島 彩乃, 野村 尚志, 栗原 佑一, 舩越 建, 梅垣 知子, 山上 淳, 久保 亮治, 天谷 雅行
    (公社)日本皮膚科学会, Mar. 2018, 日本皮膚科学会雑誌, 128(3) (3), 435 - 435, Japanese

  • ゲノム不安定性が引き起こす加齢性皮膚疾患の分子病態解析
    久保亮治, 藤田春美, 佐々木貴史, 中林一彦, 宮本達雄, 小崎健次郎
    2018, 日本分子生物学会年会プログラム・要旨集(Web), 41st

  • The identification of a postzygotic GJA1 mutation in a patient with an inflammatory linear verrucous epidermal nevus suggests that the disease is a mosaic of erythrokeratodermia variabilis et progressiva
    N. Umegaki-Arao, T. Sasaki, H. Fujita, S. Aoki, M. Amagai, M. Seishima, A. Kubo
    Oct. 2017, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 137(10) (10), S226 - S226, English
    Summary international conference

  • Tight junction barriers in sebaceous glands are crucial for proper terminal differentiation of sebocytes
    A. Kubo, T. Atsugi, M. Yokouchi, A. Hirabayashi, M. Ohyama, M. Amagai
    Oct. 2017, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 137(10) (10), S235 - S235, English
    Summary international conference

  • A mutation in the desmoglein 1 transmembrane domain abrogates lipid raft targeting and causes severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome
    J. Lewis, A. Caldara, N. Strong, J. K. Wahl, A. L. Mattheyses, M. Amagai, T. Sasaki, K. Nakabayashi, K. Hata, Y. Matsubara, A. Kubo, S. Stahley, A. Kowalczyk
    May 2017, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 137(5) (5), S94 - S94, English
    Summary international conference

  • 巨大な若年性黄色肉芽腫の1例
    新谷 悠花, 小幡 祥子, 川島 裕平, 舩越 建, 久保 亮治, 齋藤 昌孝, 大内 健嗣
    (公社)日本皮膚科学会, Apr. 2017, 日本皮膚科学会雑誌, 127(4) (4), 650 - 650, Japanese

  • 免疫チェックポイント阻害薬投与中に中枢性副腎機能不全症状を呈した悪性黒色腫の1例
    持丸 奈央子, 平井 郁子, 堀川 弘登, 内田 理美, 小幡 祥子, 久保 亮治, 海老原 全, 天谷 雅行, 栗原 勲, 舩越 建
    (一社)日本皮膚アレルギー・接触皮膚炎学会, Oct. 2016, Journal of Environmental Dermatology and Cutaneous Allergology, 10(4) (4), 415 - 415, Japanese

  • エンドキサンパルス療法、血漿交換療法を必要とした食道狭窄を伴う粘膜類天疱瘡の1例
    鳩貝 亜希, 栗原 佑一, 舩越 建, 高橋 勇人, 久保 亮治, 山上 淳, 天谷 雅行, 松田 諭, 中村 理恵子, 神戸 有希
    (公社)日本皮膚科学会, Jun. 2016, 日本皮膚科学会雑誌, 126(7) (7), 1320 - 1320, Japanese

  • Cell shape determines the regulatory mechanisms for maintaining tight junction barrier homeostasis in epidermal turnover
    M. Yokouchi, T. Atsugi, M. Kajimura, M. Suematsu, M. Furuse, M. Amagai, A. Kubo
    May 2016, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 136(5) (5), S60 - S60, English
    Summary international conference

  • 多発性子宮筋腫と皮膚平滑筋腫症を認めたHereditary Leiomyomatosis and Renal Cell Cancerの2例
    梅垣 知子, 木島 俊英, 小峰 佑奈, 伊勢 美咲, 舩越 建, 進 伸幸, 常深 祐一郎, 林 伸和, 白石 英馨, 天谷 雅行, 久保 亮治
    (公社)日本皮膚科学会, May 2016, 日本皮膚科学会雑誌, 126(5) (5), 959 - 959, Japanese

  • 幼少期に環状浮腫性紅斑を生じたepidermolysis bullosa simplex with mottled pigmentationの2例
    熊谷宜子, 熊谷宜子, 梅垣知子, 佐々木貴史, 芦田敦子, 常深祐一郎, 川島眞, 中村晃一郎, 石河晃, 天谷雅行, 天谷雅行, 久保亮治
    2016, 日本皮膚科学会雑誌, 126(5) (5)

  • Epidermolysis bullosa simplex with mottled pigmentationの2家系
    久保亮治, 熊谷宜子, 天谷雅行, 芦田敦子, 芦田敦子, 常深祐一郎, 石河晃
    2016, 日本皮膚科学会雑誌, 126(6) (6)

  • Tight junction barrier dysfunction induced by epidermis-specific claudin-1 ablation is sufficient to cause dermatitis in mice
    A. Kubo, T. Hirano, M. Yokouchi, H. Kawasaki, T. Atsugi, M. Amagai
    May 2015, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 135, S60 - S60, English
    Summary international conference

  • CHILD症候群7例におけるコレステロール生合成経路阻害による治療効果と病態形成機構の検討
    久保亮治, 梅垣知子, 藤田春美, 久保亜紀子, 吉田和恵, 森岡眞治, 林伸和, 臼田俊和, 新関寛徳, 高森建二, 石河晃, 末松誠, 天谷雅行
    2015, 日本皮膚科学会雑誌, 125(4) (4)

  • A NOVEL FRAMESHIFT MUTATION OF C.1638_1641DELCAGT IN KRT5 IN A JAPANESE FAMILY WITH EPIDERMOLYSIS BULLOSA SIMPLEX WITH MOTTLED PIGMENTATION
    Yoshiko Kumagai, Yoshio Nakamura, Takashi Sasaki, Hayato Takahashi, Masayuki Amagai, Akiharu Kubo
    Oct. 2014, JOURNAL OF DERMATOLOGY, 41, 61 - 61, English
    Summary international conference

  • Tight junction barriers are functionally organized in hair follicles and sebaceous glands
    T. Atsugi, M. Yokouchi, M. Ohyama, M. Amagai, A. Kubo
    May 2014, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 134, S63 - S63, English
    Summary international conference

  • Mutations in SERPINB7, encoding a serine protease inhibitor, cause Nagashima-type palmoplantar keratosis
    A. Kubo, A. Shiohama, T. Sasaki, K. Nakabayashi, J. Kudoh, K. Hata, A. Umezawa, Y. Tokura, A. Ishiko, H. Niizeki, K. Kabashima, Y. Mitsuhashi, M. Amagai
    May 2014, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 134, S73 - S73, English
    Summary international conference

  • 悪性黒色腫患者に生じた転移性病変との鑑別を要した二次性原発性悪性黒色腫の1例
    古市 祐樹, 舩越 建, 福田 桂太郎, 久保 亮治, 谷川 瑛子, 森下 加奈子, 木村 佳史
    (公社)日本皮膚科学会, Mar. 2014, 日本皮膚科学会雑誌, 124(3) (3), 362 - 362, Japanese

  • 角質の質量分析イメージング
    久保亮治
    Mar. 2014, 皮膚アレルギーフロンティア, 12(1) (1), 31 - 33, Japanese
    Introduction scientific journal

  • 皮膚科セミナリウム：皮膚タイトジャンクションバリア構造の詳細な理解
    久保亮治
    Mar. 2014, 日本皮膚科学会雑誌, 123(3) (3), 305 - 314, Japanese
    Introduction scientific journal

  • 特集：遺伝子検査による早期診断：疾患−表皮水疱症
    久保亮治
    東京医学社, Feb. 2014, 周産期医学, 44(2) (2), 243 - 245, Japanese
    Introduction scientific journal

  • バリア異常からみたアトピー性皮膚炎の病態と治療
    久保亮治
    Dec. 2013, 日本皮膚科学会雑誌, 123(13) (13), 2702 - 2706, Japanese
    Introduction scientific journal

  • 経皮感作はなぜ重要か？〜皮膚バリア障害からみたアトピー疾患〜
    久保亮治
    Dec. 2013, 皮膚アレルギーフロンティア, 11(3) (3), 131 - 135, Japanese
    Introduction scientific journal

  • ロクロニウムによるアナフィラキシーショックの1例
    本田 治樹, 安田 文世, 福山 雅大, 大方 詩子, 藤尾 由美, 舩越 建, 永尾 圭介, 久保 亮治, 岡本 一真, 工藤 樹彦, 四津 良平
    (公社)日本皮膚科学会, Nov. 2013, 日本皮膚科学会雑誌, 123(12) (12), 2278 - 2278, Japanese

  • 佐々木貴史, 塩濱愛子, 久保亮治, 川崎洋, 山本明美, 山田健人, 蜂矢隆久, 清水厚志, 岡野栄之, 工藤純, 天谷雅行
    「ワークショップ選出演題「ワークショップW1-6」抄録は331ページ参照」
    The Japan Society for Clinical Immunology, 31 Oct. 2013, 日本臨床免疫学会会誌, 36(5) (5), 331 - 387a, Japanese

  • The stratum corneum comprises three layers with distinct barrier properties to metal ions
    A. Kubo, I. Ishizaki, A. Kubo, H. Kawasaki, K. Nagao, Y. Ohashi, M. Amagai
    May 2013, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 133, S115 - S115, English
    Summary international conference

  • A homozygous nonsense mutation of gene for Mattrin, a component of lamellar granule secretory system, produces spontaneous dermatitis in mice
    T. Sasaki, A. Shiohama, A. Kubo, H. Kawasaki, A. Ishida-Yamamoto, T. Yamada, T. Hachiya, A. Shimizu, H. Okano, J. Kudoh, M. Amagai
    May 2013, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 133, S118 - S118, English
    Summary international conference

  • HSVの再活性化による口腔内・食道潰瘍を呈した薬剤性過敏症症候群(DIHS)の1例
    森本 亜里, 舩越 建, 福島 彩乃, 久保 亮治, 海老原 全, 永尾 圭介, 林田 哲, 真杉 洋平, 亀山 香織
    (公社)日本皮膚科学会, May 2013, 日本皮膚科学会雑誌, 123(6) (6), 1081 - 1081, Japanese

  • 皮膚バリア機能障害からみたアトピー性疾患の病態解明
    久保亮治
    Apr. 2013, 日本小児科医会会報第45号 アレルギー特集号, 45, 31 - 37, Japanese
    Introduction scientific journal

  • Yusuke Suzuki, Katsunori Masaki, Shizuko Kagawa, Hiroshi Kawasaki, Keisuke Nagao, Akiharu Kubo, Tomoko Betsuyaku, Masayuki Amagai, Koichiro Asano
    Feb. 2013, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 131(2) (2), AB239 - AB239, English
    Summary international conference

  • 皮膚バリア機能と経皮感作
    川崎洋, 久保亮治
    Feb. 2013, アレルギーの臨床, 33(2) (2), 17 - 32, Japanese
    Introduction scientific journal

  • 皮膚タイトジャンクションバリアと疾患 (第111回 日本皮膚科学会総会 : 進化する皮膚科 : 知と技を磨く) -- (教育講演 ケラチノサイトとバリア機能)
    久保 亮治
    日本皮膚科学会, Dec. 2012, 日本皮膚科学会雑誌 = The Japanese journal of dermatology, 122(13) (13), 3268 - 3270, Japanese

  • 三次元イメージングで出会う皮膚銀河の天の川
    Kubo Akiharu
    日本皮膚科学会, Dec. 2012, 日本皮膚科学会雑誌, 122(13) (13), 3697 - 3699, Japanese
    Introduction scientific journal

  • 皮膚タイトジャンクションバリアと疾患
    Kubo Akiharu
    Dec. 2012, 日本皮膚科学会雑誌, 122(13) (13), 3268 - 3270, Japanese
    Introduction scientific journal

  • 正木 克宜, 鈴木 雄介, 加川 志津子, 樹神 元博, 小熊 剛, 加畑 宏樹, 宮田 純, 田中 希宇人, 川崎 洋, 永尾 圭介, 久保 亮治, 福永 興壱, 別役 智子, 天谷 雅行, 浅野 浩一郎
    (一社)日本アレルギー学会, Oct. 2012, アレルギー, 61(9-10) (9-10), 1540 - 1540, Japanese

  • 鈴木 雄介, 正木 克宜, 加川 志津子, 川崎 洋, 永尾 圭介, 久保 亮治, 別役 智子, 天谷 雅行, 浅野 浩一郎
    (一社)日本アレルギー学会, Oct. 2012, アレルギー, 61(9-10) (9-10), 1523 - 1523, Japanese

  • 皮膚の物理的バリアと免疫のかかわり
    Kubo Akiharu
    Oct. 2012, 医学のあゆみ, 242, 774 - 779, Japanese
    Introduction scientific journal

  • 皮膚バリア機能と表皮タイトジャンクション
    久保亮治
    06 Sep. 2012, マルホ皮膚科セミナー【ラジオNIKKEI】放送内容集,, 222, 09 - 12, Japanese
    Lecture materials

  • 病変が広範囲で落葉状天疱瘡との鑑別を必要とした水疱性膿痂疹の成人例
    西村 真由子, 山上 淳, 伊勢 美咲, 吉田 哲也, 舩越 建, 久保 亮治, 永尾 圭介, 海老原 全, 天谷 雅行, 佐藤 佐由里
    (公社)日本皮膚科学会, Mar. 2012, 日本皮膚科学会雑誌, 122(3) (3), 704 - 704, Japanese

  • 全身電子線照射が著効した腫瘍期菌状息肉症の1例
    泉 映里, 大内 健嗣, 舩越 建, 久保 亮治, 谷川 瑛子, 天谷 雅行, 永尾 圭介, 川口 修, 寺木 祐一
    (公社)日本皮膚科学会, Feb. 2012, 日本皮膚科学会雑誌, 122(2) (2), 470 - 470, Japanese

  • 皮膚バリア機能異常と抗原感作 (特集 アレルギー疾患 : 感作と発症のからくり) -- (基礎研究から明らかとなった感作と発症の機序)
    久保 亮治, 天谷 雅行
    医薬ジャーナル社, Jan. 2012, アレルギー・免疫, 19(1) (1), 32 - 39, Japanese

  • 皮膚バリア構造・機能の可視化への挑戦
    久保 亮治
    日本皮膚科学会, 15 Dec. 2011, 日本皮膚科学会雑誌, 121(13) (13), 2920 - 2922, Japanese

  • Langerin-positive Langerhans cells but not Langerin-negative inflammatory dendritic epidermal cells penetrate epidermal tight junction barriers in atopic dermatitis
    Kazue Yoshida, Akiharu Kubo, Mariko Yokouchi, Ken Ishii, Hiroshi Kawasaki, Tamotsu Ebihara, Keisuke Nagao, Masayuki Amagai
    Sep. 2011, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 131, S52 - S52, English
    Summary international conference

  • Langerhans cells play an essential role in inducing protective humoral immune response subsequent to antigen uptake through tight junctions
    Takeshi Ouchi, Akiharu Kubo, Takeya Adachi, Tetsuro Kobayashi, Daniela Y. Kitashima, Hideki Fujii, Bjoern E. Clausen, Shigeo Koyasu, Masayuki Amagai, Keisuke Nagao
    Sep. 2011, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 131, S83 - S83, English
    Summary international conference

  • Epidermal barrier revisited
    久保 亮治
    科学評論社, Sep. 2011, Clinical immunology & allergology, 56(3) (3), 294 - 302, Japanese

  • Impaired stratum corneum barrier and enhanced percutaneous immune responses in filaggrin knockout mice
    H. Kawasaki, K. Nagao, A. Kubo, T. Hata, H. Mizuno, T. Yamada, M. Amagai
    Apr. 2011, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 131, S45 - S45, English
    Summary international conference

  • Human epidermal tight junctions are functional and allow penetration of activated Langerhans cell dendrites
    K. Yoshida, A. Kubo, M. Yokouchi, K. Ishii, H. Kawasaki, T. Ebihara, M. Ohyama, K. Nagao, M. Amagai
    Apr. 2011, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 131, S47 - S47, English
    Summary international conference

  • Epidermal barrier and tight junctions
    久保 亮治
    医学書院, Apr. 2011, 臨床皮膚科, 65(5) (5), 38 - 43, Japanese

  • 有棘細胞癌が多発した劣性栄養障害型表皮水疱症の1例
    土井 亜希子, 山上 淳, 舩越 建, 高江 雄二郎, 久保 亮治, 谷川 瑛子, 海老原 全, 天谷 雅行, 石河 晃
    (公社)日本皮膚科学会, Mar. 2011, 日本皮膚科学会雑誌, 121(3) (3), 585 - 585, Japanese

  • 皮膚バリア機構の新しい理解 〜体表面における防御と索敵のメカニズム〜
    久保亮治, 天谷雅行
    ヒュ-マンサイエンス振興財団, Jan. 2011, ヒューマンサイエンス, 22(1) (1), 14-18 - 18, Japanese
    Introduction commerce magazine

  • Filaggrin Knockout Mice as a Tool for Understanding Percutaneous Antigen Exposure in Barrier-disrupted Skin
    Hiroshi Kawasaki, Keisuke Nagao, Akiharu Kubo, Tsuyoshi Hata, Hideaki Mizuno, Taketo Yamada, Masayuki Amagai
    Sep. 2010, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 130, S43 - S43, English
    Summary international conference

  • 抗表皮細胞間抗体を認めるも,血中抗デスモグレイン抗体陰性の自己免疫性水疱症の1例
    今岡かおる, 澄川靖之, 高橋仁, チョウ ゾウヘイン, 山崎朋子, 河野邦江, 出来尾格, 古村南夫, 森田栄伸, 久保亮治, 天谷雅行, 福田俊平, 橋本隆
    日本皮膚科学会-西部支部, 01 Jun. 2010, 西日本皮膚科, 72(3) (3), 300 - 300, Japanese

  • How to uptake external antigens on the skin: dynamic cooperation of tight junction barriers and epidermal Langerhans cells
    久保 亮治, 天谷 雅行
    フレグランスジャーナル社, May 2010, Fragrance journal, 38(5) (5), 14 - 18, Japanese

  • Langerhans cell dendrites penetrate through epidermal tight junction barrier during foreign antigen uptake
    A. Kubo, K. Nagao, M. Yokouchi, K. Yoshida, H. Sasaki, M. Amagai
    Apr. 2010, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 130, S125 - S125, English
    Summary international conference

  • Activated Langerhans cells capture external antigens by sending their dendrites out through epidermal tight junctions
    A. Kubo, K. Nagao, M. Yokouchi, H. Sasaki, M. Amagai
    Sep. 2009, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 129, S56 - S56, English
    Summary international conference

  • Identification of novel ciliary proteins using microarray analyses of in vitro ciliogenesis
    A. Kubo, M. Amagai, S. Tsukita, S. Tsukita
    Apr. 2008, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 128, S97 - S97, English
    Summary international conference

  • Odf2/cenexin-deficient mother centrioles lack the distal/subdistal appendages and the ability to generate primary cilia
    Hiroaki Ishikawa, Akiharu Kubo, Shoichiro Tsukita, Sachiko Tsukita
    Jun. 2005, CELL STRUCTURE AND FUNCTION, 30, 56 - 56, English
    Summary international conference

  • Dynamic aspects of claudin-based tight junctions
    Shoichiro Tsukita, Miho Matsuda, Junichi Ikenouchi, Akiharu Kubo, Mikio Furuse
    May 2004, CELL STRUCTURE AND FUNCTION, 29, 3 - 3, English
    Summary international conference

■ Books And Other Publications
  • 標準皮膚科学 第11版
    久保亮治
    医学書院, Feb. 2020, 63-65 577-581, Japanese

  • Fitzpatrick’s Dermatology in General Medicine
    Kubo A, Amagai M
    Joint work, Skin Barrier, McGraw Hill Education, Mar. 2019, 206-231

  • 専門医でも聞きたい皮膚科診療100の質問
    Akiharu Kubo
    218-219, メディカルレビュー社, Jun. 2017, Japanese

  • 皮膚科研修ノート「正常皮膚の構造と機能」
    Akiharu Kubo
    123-127, 診断と治療社, Apr. 2016, Japanese

  • 水虫
    Akiharu Kubo
    講談社, Dec. 2015, Japanese
    General book

  • 皮膚科臨床アセット19「水疱性皮膚疾患」
    Kubo Akiharu
    Contributor, skin fragility症候群の病因、診断、治療, 中山書店, Mar. 2014, Japanese
    Scholarly book

  • 3D visualization of epidermal Langerhans cells
    Kubo A, Nagao K, Amagai M
    Joint work, Humana Press, Jan. 2013, English
    Scholarly book

■ Lectures, oral presentations, etc.
  • 汗孔角化症はメバロン酸経路遺伝子のセカンドヒット変異細胞がクローン増殖して炎症を引き起こす優性遺伝性疾患である
    久保亮治
    第3回日本免疫不全・自己炎症学会 総会・学術集会, Feb. 2020, Japanese, 東京

  • HCQ内服加療中に妊娠・出産したSLEの1例
    小田俊輔, 椎谷千尋, 新川宏樹, 久保亮治, 末岡浩, 仁科直, 谷川瑛子
    第888回日本皮膚科学会東京地方会（城西地区）, Jan. 2020, Japanese, 東京

  • 表皮バリアの形成機構から考えるアトピー性皮膚炎の病態と治療
    久保亮治
    日本アレルギー学会 第6回総合アレルギー講習会, Dec. 2019, 横浜

  • Homeostatic pruning and activity of epidermal nerves are dysregulated in barrier-impaired skin during chronic itch development
    Takahashi S, Ishida A, Kubo A, Kawasaki H, Ochiai S, Watanabe T, Nakayama M, Koseki H, Amagai M, Okada T
    48th Annual Meeting of the Japanese Society for Immunology, Dec. 2019, English, Hamamatsu, Japan

  • Barrier homeostasis on the skin surface
    Kubo A
    48th Annual Meeting of the Japanese Society for Immunology, Dec. 2019, English, Hamamatsu, Japan

  • EDA遺伝子に変異を認めた低汗性外胚葉形成不全症の1例
    松本幸男, 持丸奈央子, 安田葉月, 久保亮治, 吉田和恵
    第83回日本皮膚科学会 東京・東部支部合同学術大会, Nov. 2019, Japanese, 東京

  • 18番染色体長腕の片親性ダイソミーによりSERPINB7 c.796C>T変異がホモ接合となって発症した長島型掌蹠角化症の1例（合同学会賞受賞）
    早川道太郎, 田原海, 小野紀子, 青木里美, 河合智子, 中林一彦, 天谷雅行, 久保亮治
    第83回日本皮膚科学会東京・東部支部合同学術大会, Nov. 2019, Japanese, 東京

  • 皮膚疾患の理解に役立つ分子形態学
    久保亮治
    第83回日本皮膚科学会東京・東部支部合同学術大会, Nov. 2019, Japanese, 東京

  • 表皮の恒常性を維持するメカニズムと疾患
    久保亮治
    第83回日本皮膚科学会東京・東部支部合同学術大会, Nov. 2019, Japanese, 東京

  • Stepwise maturation of tight junctions on keratinocytes during cell translocation across the epidermal tight junction barrier
    Yokouchi M, Amagai M, Kubo A
    44th Annual Meeting of the Japanese Society for Investigative Dermatology, Nov. 2019, English, Aomori, japan

  • Homeostatic pruning and activity of epidermal nerves are dysregulated in barrier-impaired skin during chronic itch development
    Takahashi S, Ishida A, Kubo A, Kawasaki H, Ochiai S, Watanate T, Nakayama M, Koseki H, Amagai M, Okada T
    44th Annual Meeting of the Japanese Society for Investigative Dermatology, Nov. 2019, English, Aomori, Japan

  • Clonal expansion of second-hit cells in MVD c.746C>T mutant heterozygotes are the major cause of porokeratosis in Japan
    Kubo A, Sasaki T, Shiohama A, Aoki S, Kawai T, Nakabayashi K, Hata K, Kosaki K, Amagai M
    44th Annual Meeting of the Japanese Society for Investigative Dermatology, Nov. 2019, English, Aomori, Japan

  • A novel frameshift mutation in KRT14 causes epidermolysis bullosa simplex: therapeutic experience with topical mTOR inhibitor
    Kishibe M, Matsuo R, Minami-Hori M, Honma M, Kubo A, Ishida-Yamamoto A
    44th Annual meeting of the Japanese Society for Investigative Dermatology, Nov. 2019, English, Aomori, Japan

  • A case of congenital generalized lipodystrophy with dyschromia caused by a heterozygous recurrent mutation of LMNA gene
    Chino T, Oyama N, Utsunomiya A, Utsunomiya N, Hasegawa M, Kubo A
    44th Annual meeting of the Japanese Society for Investigative Dermatology, Nov. 2019, English, Aomori, Japan

  • Keratinocyte specific biallelic mutations in mevalonate pathway genes due to postzygotic second hits drive linear and disseminated superficial actinic porokeratosis
    Kubo A, Sasaki T, Suzuki H, Shiohama A, Aoki S, Kawai T, Nakabayashi K, Hata K, Kosaki K, Amagai M
    49th Annual Meeting of European Society for Dermatological Research(ESDR), Sep. 2019, English, Bordeaux, France

  • 高熱、皮膚粘膜症状、ぶどう膜炎で初発したBehçet病の2例
    新川宏樹, 田中諒, 田原海, 朱瀛瑤, 種瀬啓士, 舩越建, 久保亮治, 太田優, 永井紀博, 天谷雅行, 谷川瑛子
    第71回日本皮膚科学会西部支部学術大会, Sep. 2019, Japanese, 高知

  • Broad lines of Blaschkoの分布を示しPIK3CAに変異を認めた列序性表皮母斑の2例
    阿部日奈子, 佐子英梨子, 齋藤京, 山田大資, 青木里美, 塩濱愛子, 佐々木貴史, 梅垣知子, 天谷雅行, 久保亮治
    第46回皮膚かたち研究学会学術大会, Jun. 2019, Japanese, 大阪

  • Cholesterol 25-hydroxylase expressing CD4+ T cell regulates skin inflammation
    Takahashi H, Nomura H, Iriki H, Kubo A, Mukai M, Sasaki T, Mikami Y, Kanno Y, O’Shea J, Amagai M
    60th International Conference on the Bioscience of Lipids, Jun. 2019, English, Tokyo, Japan

  • 皮膚バリア機構からみたアレルギー感作・発症・炎症慢性化のメカニズム
    久保亮治
    第68回日本アレルギー学会学術大会, Jun. 2019, Japanese, 東京

  • A case of neonatal linear IgA bullous dermatosis possibly caused by IgA transferred through the breastmilk
    Kurihara Y, Tanaka C, Egami S, Yamagami J, Kubo A, Funakoshi T, Nishie W, Amagai M
    24th World Congress of Dermatology, Jun. 2019, English, Milan, Italy

  • Broad lines of Blaschkoの分布を示しPIK3CA に変異を認めた列序性表皮母斑の2例
    阿部日奈子, 梅垣知子, 小野紀子, 田中諒, 青木里美, 佐々木貴史, 齋藤京, 山田大資, 天谷雅行, 久保亮治
    第118回日本皮膚科学会総会, Jun. 2019, Japanese, 名古屋

  • ブラシュコ線に沿う表皮母斑とチェッカーボード様の色素斑が独立に別々の分布を示した2例
    佐子英梨子, 梅垣知子, 小野紀子, 田中諒, 青木里美, 佐々木貴史, 吉田和恵, 山田大資, 天谷雅行, 久保亮治
    第118回日本皮膚科学会総会, Jun. 2019, Japanese, 名古屋

  • 表皮バリアの動的恒常性から皮膚炎の病態を考える
    久保亮治
    第118回日本皮膚科学会総会, Jun. 2019, Japanese, 名古屋

  • 皮膚バリアケアによる慢性皮膚炎の治療と予防
    久保亮治
    第118回日本皮膚科学会総会, Jun. 2019, Japanese, 名古屋

  • NUDT15 polymorphism in treatment by azathioprine for pemphigus/pemphigoid patients
    Endo N, Kurihara Y, Egami S, Yamagami J, Kubo A, Amagai M
    118th Annual meeting of the Japanese Dermatological Association, Jun. 2019, English, Nagoya, Japan

  • The desmosome is a mesoscale lipid raft-like membrane domain
    Caldara AL, Lewis JD, Zimmer SE, Seybold A, Strong NL, Stahley SN, Frangakis AS, Levental I, Wahl JK, Mattheyses AL, Sasaki T, Nakabayashi K, Hata K, Matsubara Y, Ishida-Yamamoto A, Amagai M, Kubo A, Kowalczyk AP
    77th Annual Meeting of the Society for Investigative Dermatology (SID 2019), May 2019, English, Chicago, USA

  • International Eczema Council Symposium "Barrier": Basic structure of the epidermis
    Kubo A
    77th Annual Meeting of the Society for Investigative Dermatology (SID 2019), May 2019, English, Chicago, USA

  • 表皮の３次元構造から理解する皮膚の機能と疾患病態
    久保亮治
    第22回日本獣医皮膚科学会学術大会・総会, Mar. 2019, Japanese, 東京, Domestic conference

  • 天疱瘡の寛解後に水疱性類天疱瘡を発症した1例
    田原海, 古市祐樹, 新川宏樹, 齋藤昌孝, 久保亮治, 天谷雅行, 舩越建, 山上淳
    第883回日本皮膚科学会東京地方会（城西地区）, Feb. 2019, Japanese, 東京, Domestic conference

  • Decrypting the four dimensional homeostasis of the epidermis
    Kubo A
    22nd meeting of the european dermatology forum, Jan. 2019, English, Montreux, Switzerland, International conference

  • 中高年期に出現した口唇の皮疹を契機に診断された遺伝性出血性毛細血管拡張症の1例
    宮川明大, 高宮城冴子, 崎山とも, 稲積豊子, 久保亮治, 比留間淳一郎
    第882回日本皮膚科学会東京地方会（城西地区）, Jan. 2019, Japanese, 東京, Domestic conference

  • 皮膚バリア機能からみたアトピー性皮膚炎の病態と治療
    久保亮治
    第5回日本アレルギー学会総合アレルギー講習会, Dec. 2018, Japanese, 大阪, Domestic conference

  • Cholesterol 25-hydroxylase expressing CD4+ T cell regulates tissue inflammation
    Takahashi H, Nomura H, Iriki H, Kubo A, Mukai M, Sasaki T, Mikami Y, Kanno Y, O’Shea J, Amagai M
    47th Annual Meeting of the Japanese Society for Immunology, Dec. 2018, English, Fukuoka, Japan, International conference

  • 皮膚バリアの構造と恒常性を維持するしくみ〜バリアからみた慢性皮膚炎の病態と治療のヒント〜
    久保亮治
    第392回日本皮膚科学会新潟地方会, Dec. 2018, Japanese, 新潟, Domestic conference

  • 皮膚の模様を診る～乳幼児・小児の様々な母斑の診断と治療の考え方～
    久保亮治
    第392回日本皮膚科学会新潟地方会, Dec. 2018, Japanese, 新潟, Domestic conference

  • 皮膚バリアの仕組みからみた慢性皮膚炎の治療戦略
    久保亮治
    第82回日本皮膚科学会東京支部学術大会, Dec. 2018, Japanese, 東京, Domestic conference

  • 臨床医学と生物学をつなぐ ～稀少疾患の病態解析と治療戦略～
    久保亮治
    第82回日本皮膚科学会東京支部学術大会, Dec. 2018, Japanese, 東京, Domestic conference

  • Chediak-Higashi症候群の1例
    福地健祐, 龍野一樹, 坂口公祥, 佐野伸一朗, 久保亮治, 戸倉新樹
    第82回日本皮膚科学会東京支部学術大会, Dec. 2018, Japanese, 東京, Domestic conference

  • ゲノム不安定性が引き起こす加齢性皮膚疾患の分子病態解析
    久保亮治
    第41回日本分子生物学会, Nov. 2018, Japanese, 横浜, Domestic conference

  • 表皮・脂腺のバリア機構と炎症
    久保亮治
    第48回日本皮膚免疫アレルギー学会総会学術大会, Nov. 2018, Japanese, 奈良, Domestic conference

  • 齧歯類皮膚を用いた皮膚バリア学の発展（第5回野村達次賞）
    久保亮治
    第98回慶應医学会総会・シンポジウム, Nov. 2018, Japanese, 東京, Domestic conference

  • 稀少疾患の解析から未知なる皮膚を探る
    久保亮治
    第69回日本皮膚科学会中部支部学術大会, Oct. 2018, Japanese, 大阪, Domestic conference

  • 軽微な魚鱗癬と絞扼輪を伴わない掌蹠角化を呈し，ロリクリン遺伝子にc.802dupG変異をヘテロに認めた父娘例
    齋藤苑子, 田中諒, 小野紀子, 梅垣知子, 青木里美, 佐々木貴史, 永井俊弘, 天谷雅行, 久保亮治
    第69回日本皮膚科学会中部支部学術大会, Oct. 2018, Japanese, 大阪, Domestic conference

  • 皮膚バリア機構からみた皮膚炎の病態と治療のヒント
    久保亮治
    第55回日本小児アレルギー学会, Oct. 2018, Japanese, 岡山, Domestic conference

  • Barrier of the skin and skin appendages
    Kubo A
    7th Joint Meeting of SSSR & SCUR, Oct. 2018, English, Asahikawa, Japan, International conference

  • Novel compound heterozygous mutations in a Japanese patient with Hermansky-Pudlak syndrome type 3
    Saito S, Tanaka R, Ono N, Umegaki-Arao N, Sasaki T, Aoki S, Yasuhara R, Nagai T, Sonobe H, Amagai M, Kubo A
    7th Joint Meeting of SSSR & SCUR, Oct. 2018, English, Asahikawa, Japan, International conference

  • 皮膚のバリアが保たれる仕組み 〜皮膚バリア破綻が招く疾患メカニズム〜
    久保亮治
    第386回日本皮膚科学会福岡地方会, Sep. 2018, Japanese, 福岡, Domestic conference

  • 染色体の多彩異数性モザイクを認めた早老症の一例
    久保亮治
    第90回日本皮膚科学会山梨地方会（島田眞路学長日本皮膚科学会理事長退任記念）, Sep. 2018, Japanese, 山梨, Domestic conference

  • 角化症における基礎と臨床のキャッチボール
    久保亮治
    第33回角化症研究会, Jul. 2018, Japanese, 東京, Domestic conference

  • NCSTN変異を同定したfamilial acne inversaの姉妹例
    小野紀子, 田中諒, 中林一彦, 秦健一郎, 鈴木寿人, 小崎健次郎, 天谷雅行, 久保亮治
    第880回日本皮膚科学会東京支部合同臨床地方会, Jul. 2018, Japanese, 東京, Domestic conference

  • 顆粒層のケラチンイメージングによる表皮角化時の細胞骨格の形態変化
    臼井景子, 松井毅, 古市祐樹, 葛野菜々子, 川崎洋, 久保亮治, 岡田峰陽, 天谷雅行
    第39回日本炎症・再生医学会, Jul. 2018, Japanese, 東京, Domestic conference

  • 小児のアトピー性皮膚炎：病態から予防・治療を考える
    久保亮治
    第42回日本小児皮膚科学会学術大会, Jul. 2018, Japanese, 東京, Domestic conference

  • 未診断の母から出生した新生児尋常性天疱瘡の１例
    田中諒, 栗原佑一, 齋藤苑子, 舩越建, 山上淳, 中崎寿隆, 松崎陽平, 天谷雅行, 久保亮治
    第42回日本小児皮膚科学会学術大会, Jul. 2018, Japanese, 東京, Domestic conference

  • 体表のバリア構造を一定に保つ仕組み
    久保亮治
    第39回日本炎症・再生医学会, Jul. 2018, Japanese, 東京, Domestic conference

  • 染色体分配異常を伴う新規早老症患者におけるCDC20遺伝子変異の同定と分子病態の解析
    藤田春美, 佐々木貴史, 宮本達雄, 森毅彦, 中林一彦, 秦健一郎, 松浦伸也, 松原洋一, 天谷雅行, 久保亮治
    第39回日本炎症・再生医学会, Jul. 2018, Japanese, 東京

  • 顔面・頸部に症状を呈する成人アトピー性皮膚炎患者における遺伝子バリアントの同定
    関口文世, 塩濱愛子, 川崎洋, 海老原全, 久保亮治, 天谷雅行, 佐々木貴史
    第39回日本炎症・再生医学会, Jul. 2018, Japanese, 東京, Domestic conference

  • 皮膚の瑞々しさを作り出す表皮細胞のかたち
    久保亮治
    第43回日本香粧品学会, Jun. 2018, Japanese, 東京, Domestic conference

  • 関節可動域の経時的な測定で病勢を評価しえた好酸球性筋膜炎の1例
    朝比奈泰彦, 新川宏樹, 齋藤苑子, 田中諒, 舩越建, 久保亮治
    第879回日本皮膚科学会東京地方会（城西地区）, Jun. 2018, Japanese, 東京, Domestic conference

  • 再発性陰部ヘルペスを契機に診断し得た選択的IgM欠損症の1例
    鎌田亜紀, 田中諒, 舩越建, 久保亮治, 天谷雅行, 谷川瑛子
    第879回日本皮膚科学会東京地方会（城西地区）, Jun. 2018, Japanese, 東京, Domestic conference

  • Structure and function of tight junctions in the epidermis and sebaceous glands
    Kubo A
    13th Meeting of the German-Japanese Society for Dermatology, Jun. 2018, English, Rottach-Egern, Germany, International conference

  • 皮膚バリア機構からみたアトピー性皮膚炎の病態と治療戦略
    久保亮治
    第117回日本皮膚科学会総会, May 2018, Japanese, 広島, Domestic conference

  • 時間軸が解き明かす皮膚三次元構造の新しい理解
    久保亮治
    第117回日本皮膚科学会総会, May 2018, Japanese, 広島, Domestic conference

  • イミキモド外用後に生じた尋常性乾癬の1例
    渡辺絵美子, 大方詩子, 久保亮治, 亀山香織, 梅垣知子, 宮川俊一
    第117回日本皮膚科学会総会, May 2018, Japanese, 広島, Domestic conference

  • ４次元で理解する表皮の恒常性を維持するしくみ
    久保亮治
    第117回日本皮膚科学会総会, May 2018, Japanese, 広島, Domestic conference

  • 多発する被角血管腫から疑われたFabry病の1例
    柳澤絵里加, 田中諒, 大内結, 徳山博文, 脇野修, 伊藤裕, 久保亮治, 山上淳
    第878回日本皮膚科学会東京地方会（城西地区）, May 2018, Japanese, 東京, Domestic conference

  • 鼻翼部と内眼角に皮膚潰瘍を生じ治療に難渋した慢性肉芽腫症の1例
    増田容子, 平井郁子, 柳澤絵里加, 栗原佑一, 舩越建, 山上淳, 櫻岡浩一, 天谷雅行, 久保亮治
    第878回日本皮膚科学会東京地方会（城西地区）, May 2018, Japanese, 東京, Domestic conference

  • Decrypting the complex barrier system of mammalian skin
    Kubo A
    International Investigative Dermatology 2018, May 2018, English, Orland, USA, International conference

  • Genetic variants in TLR1, TIRAP and PSAPL1 are enriched in a specific subgroup of adult atopic dermatitis showing persistent skin manifestation on the face and neck area
    Yasuda-Sekiguchi F, Shiohama A, Kawasaki H, Ebihara T, Kubo A, Amagai M, Sasaki T
    International Investigative Dermatology 2018, May 2018, English, Orlando, USA, International conference

  • Imaging of the epidermal nerve dynamics and activity in the normal and pruritic dermatitis conditions
    Takahashi S, Ishida A, Kawasaki H, Kubo A, Amagai M, Okada T
    International Investigative Dermatology 2018, May 2018, English, Orlando, USA, International conference

  • Tmem79 deficient mice sequentially develop dermatitis associated with S.aureus non-dominant and dominant dysbioses
    Sasaki T, Shiohama A, Matsuda K, Watanabe H, Yamada T, Kawasaki H, Kubo A, Amagai M
    International Investigative Dermatology 2018, May 2018, English, Orlando, USA, International conference

  • Identification and molecular characterization of a CDC20 mutation in a novel mosaic variegated aneuploidy syndrome with premature aging phenotypes
    Fujita H, Sasaki T, Miyamoto T, Mori T, Nakabayashi K, Hata K, Matsuura S, Matsubara Y, Amagai M, Kubo A
    International Investigative Dermatology 2018, May 2018, Orlando, USA, International conference

  • 形態観察から考える皮膚バリア機能と障害 ～アトピー性皮膚炎から水疱症まで～
    久保亮治
    第34回日本皮膚病理組織学会総会・学術大会, Apr. 2018, Japanese, 東京, Domestic conference

  • 表皮母斑を認めるモザイク症例における原因遺伝子検索の検討
    久保亮治, 佐々木貴史, 梅垣知子, 吉田和恵, 新関寛徳, 立石千晴, 鶴田大輔, 天谷雅行
    第25回分子皮膚科学フォーラム, Apr. 2018, Japanese, 函館, Domestic conference

  • Tight but dynamic: the sophisticated barrier system of mammalian skin
    Kubo, A
    3rd Singapore International Conference on Skin Research & 9th Pan Asian-Pacific Skin Barrier Symposium, Mar. 2018, English, Singapore

  • 乾癬様の爪病変を伴った好酸球性膿疱性毛包炎の2例
    梅垣知子, 種本紗枝, 久保 亮治, 高橋勇人, 栗原佑一, 髙杉亜里紗, 柳澤絵里加, 齋藤昌孝, 天谷雅行
    第466回日本皮膚科学会大阪地方会（片山一朗教授退官記念地方会）, Mar. 2018, Japanese, 大阪

  • Cholesterol 25-hydroxylase expressing CD4+ T cell regulates skin inflammation
    Takahashi H, Nomura H, Iriki H, Kubo A, Mukai M, Sasaki T, Mikami Y, O’Shea J, Amagai M
    International Investigative Dermatology 2018, Feb. 2018, English, Orlando, USA, International conference

  • アザチオプリン内服で汎血球減少と成長期脱毛を生じた尋常性天疱瘡の1例
    鎌田亜紀, 福島彩乃, 野村尚志, 栗原佑一, 舩越建, 梅垣知子, 山上淳, 久保 亮治, 天谷雅行
    第876回日本皮膚科学会東京地方会（城西地区）, Dec. 2017, Japanese, 東京

  • A familial case of nail patella syndrome with a heterozygous indel mutation of LMX1B detected by sequencing and luciferase reporter assay
    Mukai, M. Fujita, H. Umegaki-Arao, N. Sasaki, T. Yasuda-Sekiguchi, F. Isojima, T. Kitanaka, S. Amagai, M. Kubo, A
    42nd Annual Meeting of the Japanese Society for Investigative Dermatology, Dec. 2017, English, Kochi, Japan

  • 皮膚バリアの精緻な仕組み 〜バリアの形成・維持機構から皮膚疾患を考える〜
    Akiharu Kubo
    第81回日本皮膚科学会東京支部学術大会, Nov. 2017, Japanese, 東京

  • NF1変異の体細胞モザイクを認めたsegmental neurofibromatosisの2例
    入來景悟, 梅垣知子, 角田梨沙, 佐々木貴史, 天谷雅行, 浜本康夫, 中山ロバート, 久保 亮治
    第81回日本皮膚科学会東京支部学術大会, Nov. 2017, Japanese, 東京

  • Rhabdomyomatous mesenchymal hamartoma(RMH)の1例
    椎山理恵, 栗原佑一, 小野紀子, 大内健嗣, 石橋正史, 天谷雅行, 久保 亮治
    第81回日本皮膚科学会東京支部学術大会, Nov. 2017, Japanese, 東京

  • Azathioprine-induced anagen effluvium and leukopenia associated with NUDT15 polymorphisms
    Nomura, H. Kurihara, Y. Saito, M. Yamagami, J. Funakoshi, T. Amagai, M. Umegaki-Arao, N. Kubo, A
    10th World Congress for Hair Research, Oct. 2017, English, Kyoto, Japan

  • 皮膚バリアの恒常性を維持する精緻なしくみ
    Akiharu Kubo
    第69回日本皮膚科学会西部支部学術大会, Oct. 2017, Japanese, 熊本

  • 列序性表皮母斑における遺伝子変異と表現型の検討
    久保 亮治, 小野紀子, 梅垣知子, 海老原全, 佐々木貴史, 藤山幹子, 新川宏樹, 齋藤京, 石河亜紀子, 櫻岡浩一, 田中諒, 新関寛徳, 天谷雅行
    第69回日本皮膚科学会西部支部学術大会, Oct. 2017, Japanese, 熊本

  • Curth-Macklin型豪猪皮状魚鱗癬の1例
    水谷友哉, 仁木真理子, 平場一美, 久保 亮治, 山本明美
    第69回日本皮膚科学会西部支部学術大会, Oct. 2017, Japanese, 熊本

  • CHST14変異(デルマタン4-O-硫酸基転移酵素-1 欠損)によるEhlers-Danlos症候群の1例
    持丸奈央子, 梅垣知子, 佐々木貴史, 小林秀, 天谷雅行, 久保 亮治
    第68回日本皮膚科学会中部支部学術大会, Oct. 2017, Japanese, 京都

  • 慢性そう痒皮膚炎における感覚神経イメージング
    高橋苑子, 石田梓, 川崎洋, 久保 亮治, 天谷雅行, 岡田峰陽
    第45回日本臨床免疫学会総会, Sep. 2017, Japanese, 東京

  • Tight junction barriers in sebaceous glands are crucial for proper terminal differentiation of sebocytes
    Kubo, A. Atsugi, T. Yokouchi, M. Hirabayashi, A. O’hyama, M. Amagai, M
    47th Annual Meeting of the European Society of Dermatological Research, Sep. 2017, English, Salzburg, Austria

  • The identification of a postzygotic GJA1 mutation in a patient with an inflammatory linear verrucous epidermal nevus suggests that the disease is a mosaic of erythrokeratodermia variabilis et progressiva
    Umegaki-Arao, N. Sasaki, T. Fujita, H. Aoki, S. Amagai, M. Seishima, M. Kubo, A
    47th Annual Meeting of the European Society of Dermatological Research, Sep. 2017, English, Salzburg, Austria

  • BCG接種後に生じた丘疹状結核疹の1例
    増田容子, 小幡祥子, 肥沼悟郎, 天谷雅行, 久保 亮治
    第874回日本皮膚科学会東京地方会（城西地区）, Sep. 2017, Japanese, 東京

  • Epidermal tight junction barrier homeostasis based on the three-dimensional cell shape of granular layer cells
    Kubo, A
    32nd Annual Meeting of the Japanese Society for Psoriasis Research, Sep. 2017, English, Tokyo, Japan

  • 末端黒子型悪性黒色腫が多発した長島型掌蹠角化症
    足立晃正, 小宮根真弓, 前川武雄, 村田哲, 塩濱愛子, 久保 亮治
    第32回角化症研究会, Aug. 2017, Japanese, 東京

  • 皮膚脂腺におけるタイトジャンクションバリアの局在と機能
    厚木徹, 横内麻里子, 平林愛, 大山学, 天谷雅行, 久保 亮治
    第38回日本炎症・再生医学会, Jul. 2017, Japanese, 大阪

  • 表皮水疱症が疑われた新生児線状IgA水疱性皮膚症の1例
    鈴木千尋, 栗原佑一, 山上淳, 久保 亮治, 舩越建, 西江渉, 松村和哉, 松島崇浩, 天谷雅行
    第39回水疱症研究会, Jul. 2017, Japanese, 札幌

  • 臨床症状より当初Epidermolysis bullosa simplex with migratory circinate erythemaを考えた単純型先天性表皮水疱症の１例
    向井美穂, 梅垣知子, 佐々木貴史, 天谷雅行, 久保 亮治
    第44回皮膚かたち研究学会学術大会, Jul. 2017, Japanese, 名古屋

  • アトピー性皮膚炎として治療されていた長島型掌蹠角化症の3例
    山内あい子, 久保 亮治, 深井和吉, 鶴田大輔
    第41回日本小児皮膚科学会学術大会, Jul. 2017, Japanese, 福井

  • ケラチン9の新規遺伝子変異を認めたVörner型掌蹠角化症の1例
    福永淑恵, 久保 亮治, 佐々木貴史, 深井和吉, 鶴田大輔
    第41回日本小児皮膚科学会学術大会, Jul. 2017, Japanese, 福井

  • 細胞の立体形状を利用した表皮バリア維持の精緻なしくみ
    Akiharu Kubo
    第66回日本アレルギー学会学術大会, Jun. 2017, Japanese, 東京

  • 表皮バリア機構からみたアトピー性皮膚炎とアトピーマーチ
    Akiharu Kubo
    第116回日本皮膚科学会総会・学術大会, Jun. 2017, Japanese, 仙台

  • 表皮バリアの恒常性を維持するしくみ
    Akiharu Kubo
    第116回日本皮膚科学会総会・学術大会, Jun. 2017, Japanese, 仙台

  • 細胞間の話しあいが生みだす美しいかたち
    Akiharu Kubo
    第116回日本皮膚科学会総会・学術大会, Jun. 2017, Japanese, 仙台

  • 遺伝性疾患における病態生理に基づいた新しい治療法
    Akiharu Kubo
    第116回日本皮膚科学会総会・学術大会, Jun. 2017, Japanese, 仙台

  • 専門医試験に出題されるであろう遺伝性皮膚疾患 〜臨床像と遺伝子のポイント〜
    Akiharu Kubo
    第116回日本皮膚科学会総会・学術大会, Jun. 2017, Japanese, 仙台

  • Brooke-Spiegler症候群の1例
    Akiharu Kubo
    第116回日本皮膚科学会総会・学術大会, Jun. 2017, Japanese, 仙台

  • GJA1モザイク変異を同定したInflammatory linear verrucous epidermal nevusの世界第1例
    Akiharu Kubo
    第116回日本皮膚科学会総会・学術大会, Jun. 2017, Japanese, 仙台

  • Genetic characterizaion of a patient with a progeroid phenotype and mosaic variegated aneuploidy
    Fujita, H. Sasaki, T. Miyamoto, T. Mori, T. Nakabayashi, K. Hata, K. Matsuura, S. Matsubara, Y. Amagai, M. Kubo, A
    Keystone Symposia/Aging and Mechanisms of Aging-Related Disease, May 2017, English, Yokohama, Japan

  • Causative gene identification and pathogenesis-based therapies in genodermatoses
    Kubo, A
    Gordon Research Conference "Epithelial Interactions in Development, Homeostasis, Disease and Therapy", May 2017, English, Lucca, Italy

  • A mutation in the desmoglein 1 transmembrane domain abrogates lipid raft targeting and cause severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome
    Lewis, J. Caldara, A. Strong, N. Wahl, J. K. Mattheyses, A. L. Amagai, M. Sasaki, T. Nakabayashi, K. Hata, K. Matsubara, Y. Kubo, A. Stahley, S. Kowalczyk, A
    76th Annual Meeting of Society for Investigative Dermatology, Apr. 2017, English, Portland, USA

  • DPP-4阻害薬関連水疱性類天疱瘡の標的抗原と臨床像
    Akiharu Kubo
    第33回千葉県皮膚科医会・日本臨床皮膚科医会千葉県支部学術講演会, Apr. 2017, Japanese, 千葉

  • 爪乾癬の診断と治療法に関する検討
    Akiharu Kubo
    第80回日本皮膚科学会東京支部学術大会, Feb. 2017, Japanese, 横浜
    Oral presentation

  • 片側性やブラシュコ線に沿った分布を示す小児皮膚疾患 〜診断と遺伝子検査のポイント〜
    Akiharu Kubo
    第80回日本皮膚科学会東京支部学術大会, Feb. 2017, Japanese, 横浜
    Invited oral presentation

  • 巨大な若年性黄色肉芽腫の1例
    Akiharu Kubo
    第871回日本皮膚科学会東京地方会（城西地区）, Jan. 2017, Japanese, 東京
    Oral presentation

  • バリア機能と皮膚免疫
    Akiharu Kubo
    第3回日本アレルギー学会総合アレルギー講習会, Dec. 2016, Japanese, 横浜

  • Epidermal barrier homeostasis and its breakage in skin diseases
    Kubo, A
    41st Annual Meeting of the Japanese Society for Investigative Dermatology, Dec. 2016, English, Sendai, Japan

  • Epidermal cell turnover across tight junctions based on Kelvin’s tetrakaidecahedron cell shape
    Kubo, A
    2nd International Symposium on ‘Autoinflammation breaks Barriers’, Nov. 2016, English, Munster, Germany

  • Clinical severity scores (PDAI/BPDAI) as a guide for treatment plan in pemphigus and pemphigoid
    Kurihara, Y. Yamagami, J. Funakoshi, T. Takahashi, H. Umegaki, N. Ouchi, T. Kubo, A. Tanikawa, A. Amagai, M
    4th Eastern Asia Dermatology Congress, Nov. 2016, English, Chiba, Japan

  • A novel mosaic variegated aneuploidy syndrome showing an early-aging phenotype
    Fujita, H. Kubo, A. Sasaki, T. Miyamoto, T. Mori, T. Nakabayashi, K. Hata, K. Matsuura, S. Matsubara, Y. Amagai, M
    27th CDB meeting Body Surface Tactics Cellular crosstalk for the generation of super-biointerface, Nov. 2016, English, Kobe, Japan
    Oral presentation

  • Spatiotemporal orchestration of epidermal cell turnover based on Kelvin’s tetrakaidecahedron cell shape
    Kubo, A
    27th CDB meeting Body Surface Tactics Cellular crosstalk for the generation of super-biointerface, Nov. 2016, English, Kobe, Japan

  • 免疫チェックポイント阻害薬投与中に中枢性副腎機能不全症状を呈した悪性黒色腫の1例
    Akiharu Kubo
    第46回日本皮膚アレルギー・ 接触皮膚炎学会総会学術大会, Nov. 2016, Japanese, 東京

  • キニーネが原因と考えられた多発性固定疹の1例
    Akiharu Kubo
    第46回日本皮膚アレルギー・接触皮膚炎学会総会学術大会, Nov. 2016, Japanese, 東京

  • Clinical features of dipeptidyl peptidase-IV (DPP-4) inhibitors associated bullous pemphigoid (BP) experienced in Keio University
    Horikawa, H. Kurihara, Y. Yamagami, J. Funakoshi, T. Umegaki-Arao, N. Takahashi, H. Kubo, A. Izumi, K. Nishie, W. Amagai, M
    The Post-Congress of 12th German-Japanese Society of Dermatology, Oct. 2016, English, Tokyo, Japan
    Oral presentation

  • Clinical features of dipeptidyl peptidase-IV (DPP-4) inhibitors associated bullous pemphigoid (BP) experienced in Keio University
    Horikawa, H. Kurihara, Y. Yamagami, J. Funakoshi, T. Umegaki-Arao, N. Takahashi, H. Kubo, A. Izumi, K. Nishie, W. Amagai, M
    12th Meeting of the German-Japanese Society of Dermatology, Oct. 2016, English, Nagano, Japan
    Oral presentation

  • Homeostasis and dysfunction of the epidermal barriers
    Kubo, A
    12th Meeting of the German-Japanese Society of Dermatology, Oct. 2016, English, Nagano, Japan

  • 口腔に発症した白色海綿状母斑の臨床的的検討
    Akiharu Kubo
    第26回日本口腔内科学会・第29回日本口腔診断学会合同学術大会, Sep. 2016, Japanese, 岡山

  • Epidermal cell turnover across tight junctions based on Kelvin’s tetrakaidecahedron cell shape
    Kubo, A
    14th Meeting of the European Epidermal Barrier Research Network, Sep. 2016, English, Munich, Germany

  • E-cadherin intergrates EGFR signaling and mechanotransduction to control tissue polarization and barrier formation
    Rübsam, M. Mertz, A. Kubo, A. Dufresne, E.R. Horsley, V. Ziegler, W. Wickström, S. A. Amagai, M. Niessen, A. C
    46th Annual Meeting of the European Society for Dermatological Research, Sep. 2016, English, München, Germany
    Oral presentation

  • Novel immune regulation by CD4+ T cells via cholesterol 25-hydroxylase pathway
    Takahashi, H. Nomura, H. Iriki, H. Kubo, A. Mikami, Y. Kanno, Y. O’Shea, J. Amagai, M
    46th Annual Meeting of the European Society for Dermatological Research, Sep. 2016, English, München, Germany
    Oral presentation

  • グリコール酸ピーリングにより皮膚症状が改善したFGFR3変異による全身性黒色表皮腫の母娘例および孤発例
    Akiharu Kubo
    第34回日本美容皮膚科学会総会学術大会, Aug. 2016, Japanese, 東京
    Oral presentation

  • 遺伝子検査にて長島型掌蹠角化症と診断した1例
    Akiharu Kubo
    第40回日本小児皮膚科学会・学術大会, Jul. 2016, Japanese, 広島
    Oral presentation

  • タクロリムス軟膏外用が白色斑に有効であったParry-Romberg症候群の1例
    Akiharu Kubo
    第40回日本小児皮膚科学会・学術大会, Jul. 2016, Japanese, 広島
    Oral presentation

  • なぜペンギンはしもやけにならないの？ 〜生物の環境適応戦略から考える皮膚の発生と多様性〜
    Akiharu Kubo
    第40回日本小児皮膚科学会・学術大会, Jul. 2016, Japanese, 広島
    Invited oral presentation

  • 後天性全身性脂肪萎縮症とるい痩との鑑別において電子顕微鏡的観察が有効であった1例
    Akiharu Kubo
    第43回皮膚のかたち研究学会学術大会, Jun. 2016, Japanese, 東京

  • LIPH c.736T>A変異による常染色体劣性縮毛症・乏毛症の臨床的重症度に寄与する因子についてのイメージ解析を用いた同定
    Akiharu Kubo
    第43回皮膚のかたち研究学会学術大会, Jun. 2016, Japanese, 東京
    Oral presentation

  • SLCO2A1変異を同定した肥厚性皮膚骨膜症の1家系
    Akiharu Kubo
    第866回日本皮膚科学会東京地方会（城西地区）, Jun. 2016, Japanese, 東京

  • 皮膚タイトジャンクションバリアとアトピー性皮膚炎
    Akiharu Kubo
    第65回日本アレルギー学会学術大会, Jun. 2016, Japanese, 東京
    Invited oral presentation

  • 染色体分配異常を伴う新規早老症の解析
    Akiharu Kubo
    第37回日本炎症・再生医学会, Jun. 2016, Japanese, 京都
    Oral presentation

  • 皮膚表皮タイトジャンクションバリアの恒常性維持機構の解析
    Akiharu Kubo
    第37回日本炎症・再生医学会, Jun. 2016, Japanese, 京都
    Invited oral presentation

  • 遊走性環状紅斑型単純型表皮水疱症の2例
    Akiharu Kubo
    第115回日本皮膚科学会総会, Jun. 2016, Japanese, 京都
    Oral presentation

  • 多発性子宮筋腫と皮膚平滑筋腫症を認めたHereditary Leiomyomatosis and Renal Cell Cancerの2例
    Akiharu Kubo
    第115回日本皮膚科学会総会, Jun. 2016, Japanese, 京都
    Oral presentation

  • カナキムマブ投与で膨疹が抑制されたクリオピリン関連周期熱症候群患者の血清中miRNA変動
    Akiharu Kubo
    第115回日本皮膚科学会総会, Jun. 2016, Japanese, 京都

  • 皮膚バリア障害の病態 〜遺伝性疾患からアトピー性皮膚炎まで〜
    Akiharu Kubo
    第115回日本皮膚科学会総会, Jun. 2016, Japanese, 京都
    Invited oral presentation

  • 遺伝性角化症の最近のトピックス 〜あたらしい疾患、あたらしい原因遺伝子、あたらしい治療〜
    Akiharu Kubo
    第115回日本皮膚科学会総会, Jun. 2016, Japanese, 京都
    Invited oral presentation

  • 長島型掌蹠角化症の遺伝子変異解析
    Akiharu Kubo
    第115回日本皮膚科学会総会, Jun. 2016, Japanese, 京都
    Invited oral presentation

  • Tissue polarization of mechano-adhesive signals, cytoskeleton and EGFR signaling controls skin barrier formation
    Ruebsam, M. Mertz, A. Goranci, G. Horsley, V. Dufresne, E. Ziegler, W. Kubo, A. Amagai, M. Niessen, C. M
    75th Annual Meeting of the Society for Investigative Dermatology, May 2016, English, Scottsdale, Arizona, USA
    Oral presentation

  • Cell shape determines the regulatory mechanisms for maintaining tight junction barrier homeostasis in epidermal turnover
    Yokouchi, M. Atsugi, T. Kajimura, M. Suematsu, M. Furuse, M. Amagai, M. Kubo, A
    75th Annual Meeting of the Society for Investigative Dermatology, May 2016, English, Scottsdale, Arizona, USA
    Oral presentation

  • Claudin-1欠損マウスを用いた脂腺タイトジャンクションバリアの解析
    Akiharu Kubo
    第23回分子皮膚科学フォーラム, Apr. 2016, Japanese, 大阪

  • 皮膚バリアの生物学 〜遺伝性疾患からアトピー性皮膚炎まで〜
    Akiharu Kubo
    第83回日本皮膚科学会山梨地方会, Apr. 2016, Japanese, 山梨
    Invited oral presentation

  • 片側性・列序性に分布する表皮母斑・掌蹠角化・縮毛を認めた列序性表皮母斑の一例
    久保 亮治, 本多皓, 梅垣知子, 塩濱愛子, 佐々木貴史, 谷川瑛子, 天谷雅行
    第275回日本皮膚科学会東海地方会, Mar. 2016, Japanese, 愛知

  • Epidermal barrier homeostasis and its breakage in skin diseases
    Kubo, A
    10th Annual Symposium in Institute of Human-Environment Interface Biology, Feb. 2016, English, Seoul, Korea

  • エンドキサン®パルス療法、血漿交換療法が奏効した食道狭窄を伴う粘膜類天疱瘡の1例
    鳩貝亜希, 栗原佑一, 舩越建, 高橋勇人, 久保 亮治, 山上淳, 中村理恵子, 神戸有希, 天谷雅行
    第79回日本皮膚科学会東京・東部支部合同学術大会, Feb. 2016, Japanese, 東京

  • 長島型掌蹠角化症：SERPINB7新規ミスセンス変異p.P277Lの解析
    久保 亮治, 塩濱愛子, 佐々木貴史, 坂部純一, 伊藤泰介, 磯田英華, 善家由香理, 中野敏明, 前田龍郎, 清島真理子, 石河晃, 椛島健治, 戸倉新樹, 天谷雅行
    第373回日本皮膚科学会岩手地方会（赤坂英俊教授退任記念学会）, Feb. 2016, Japanese, 岩手

  • Homeostatic cell turnover mechanisms that maintain tight junction barrier integrity in the epidermis
    Yokouchi, M. Kajimura, M. Suematsu, M. Furuse, M. Amagai, M. Kubo, A
    6th Annual Congress of Pan AsianPacific Skin Barrier Research Society PAPSBRS, Dec. 2015, English, Okayama, Japan

  • Functional tight junction barriers in sebaceous glands: defects in holocrine secretion in claudin-1 deficient mice
    Atsugi, T. Yokouchi, M. Hirabayashi, A. Ohyama, M. Amagai, M. Kubo, A
    40th Annual Meeting of the Japanese Society for Investigative Dermatology, Dec. 2015, English, Okayama, Japan

  • Clinicopathological insights into the phenotypic variation of autosomal recessive hypotrichosis/wooly hair by c.736T>A LIPH mutation
    Ise, M. Kubo, A. Sasaki, T. Umegaki-Arao, N. Amagai, M. Ohyama, M
    40th Annual Meeting of the Japanese Society for Investigative Dermatology, Dec. 2015, English, Okayama, Japan

  • Classical cadherins control polarized organization of junctions and cytoskeleton in stratified epithelia
    Rubsam, M. Kubo, A. Mertz, A. Boggetti, B. Goranci, G. Dufresne, E. Horsley, V. Amagai, M. Niessen, C
    40th Annual Meeting of the Japanese Society for Investigative Dermatology, Dec. 2015, English, Okayama, Japan

  • Characterization of the centrosome cycle in normal human epidermis, Bowen’s disease, and squamous cell carcinoma.
    Watanuki, S. Atsugi, T. Hirano, T. Tanese, K. Kouyama, K. Amagai, M. Kubo, A
    40th Annual Meeting of the Japanese Society for Investigative Dermatology, Dec. 2015, English, Okayama, Japan

  • 長島型掌蹠角化症の1例
    祖川麻衣子, 木下華子, 広瀬憲志, 久保宜明, 久保 亮治
    第144回日本皮膚科学会徳島地方会, Dec. 2015, Japanese, 徳島

  • Clinical, histological and genetic insights into the pathophysiology underlying phenotypic variation of autosomal recessive hypotrichosis/wooly hair caused by c.736T>A LIPH mutation
    Ise, M. Kubo, A. Umegaki, N. Amagai, M. Ohyama, M
    9th World Congress for Hair Research, Nov. 2015, English, Miami, USA

  • Vicious cycle in atopic dermatitis: Epidermal barriers, Allergic sensitization and inflammation
    Kubo, A
    44th Annual Meeting of the Japanese Society for Immunology, Nov. 2015, English, Sapporo, Japan

  • アトピー性皮膚炎表皮におけるタイトジャンクションバリアと樹状細胞の解析
    久保 亮治
    第43回日本臨床免疫学会総会, Oct. 2015, Japanese, 兵庫

  • COL17A1変異による非ヘルリッツ型接合部型表皮水疱症と診断した１例
    井上雅子, 森下佳子, 佐々木貴史, 久保 亮治, 青山裕美
    第67回日本皮膚科学会西部支部学術大会, Oct. 2015, Japanese, 長崎

  • PORCNの片アレル欠失によるGoltz症候群(focal dermal hypoplasia)の１例
    小野紀子, 佐々木貴史, 亀山香織, 貴志和生, 石河晃, 天谷雅行, 久保 亮治
    第67回日本皮膚科学会西部支部学術大会, Oct. 2015, Japanese, 長崎

  • 集族性ざ瘡として治療されていたComedonal Darier’s disease
    多田明子, 澤田文久, 牧野英一, 久保 亮治, 物部泰昌, 青山裕美
    第67回日本皮膚科学会西部支部学術大会, Oct. 2015, Japanese, 長崎

  • PET-CTで患側膝部に滑膜炎による異常集積を認めた病期ⅢC足趾悪性黒色腫の1例
    雪野祐莉子, 栗原佑一, 久保 亮治, 舩越建, 安西秀美, 菊田一貴, 森岡秀夫, 八代聖
    第862回日本皮膚科学会東京地方会（城西地区）, Sep. 2015, Japanese, 東京

  • タイトジャンクションバリアの恒常性を維持しながら、表皮細胞は如何にターンオーバーするのか
    横内麻里子, 梶村眞弓, 末松誠, 天谷雅行, 久保 亮治
    第36回日本炎症・再生医学会, Jul. 2015, Japanese, 東京

  • Tmem79欠損マウスは黄色ブドウ球菌増殖を伴う部位特異的皮膚炎を自然発症する
    佐々木貴史, 塩濱愛子, 安田文世, 久保 亮治, 川崎洋, 松井毅, 天谷雅行
    第36回日本炎症・再生医学会, Jul. 2015, Japanese, 東京

  • 小児の下腿の皮膚に生じたPretibial lymphoplasmacytic plaque in childrenの1例
    向井美穂, 種瀬啓士, 高橋勇人, 久保 亮治, 天谷雅行
    第39回日本小児皮膚科学会学術大会, Jul. 2015, Japanese, 鹿児島

  • 羊膜索症候群を合併した優性栄養障害型表皮水疱症の1例
    崎山とも, 梅垣知子, 佐々木貴史, 小崎健次郎, 天谷雅行, 久保 亮治
    第39回日本小児皮膚科学会学術大会, Jul. 2015, Japanese, 鹿児島

  • 皮膚角層バリアの進化と機能
    久保 亮治
    第39回日本小児皮膚科学会学術大会, Jul. 2015, Japanese, 鹿児島

  • 角化重層上皮におけるタイトジャンクションバリアの恒常性を維持した細胞ターンオーバーメカニズム
    久保 亮治, 横内麻里子, 天谷雅行
    第67回日本細胞生物学会大会, Jun. 2015, Japanese, 東京

  • 壮年期に発症した躯幹四肢の網状色素斑と脱色素斑
    馬場裕子, 種瀬啓士, 久保 亮治
    第31回日本皮膚病理組織学会学術大会, Jun. 2015, Japanese, 東京

  • 皮膚が備えるバリア機構とその破綻の病態生理
    久保 亮治
    第87回日本皮膚科学会群馬地方会, Jun. 2015, Japanese, 群馬

  • CD30-positive lymphoproliferative disorder arising in a mycosis fungoides patient in long-term remission
    Baba, Y. Tanese, K. Funakoshi, T. Kubo, A
    23rd World Congress of Dermatology, Jun. 2015, English, Vancouver, Canada

  • Tight junctions, the skin barrier and atopic dermatitis
    Kubo, A
    23rd World Congress of Dermatology, Jun. 2015, English, Vancouver, Canada

  • CHILD症候群7例におけるコレステロール生合成経路阻害による治療効果と病態形成機構の検討
    久保 亮治, 梅垣知子, 藤田春美, 久保亜紀子, 森岡眞治, 林伸和, 臼田俊和, 新関寛徳, 高森建二, 石河晃, 末松誠, 天谷雅行
    第114回日本皮膚科学会総会, May 2015, Japanese, 神奈川

  • ケミカルピーリングにより皮膚症状が改善したFGFR3変異による家族性全身性黒色表皮腫の母娘例
    市山進, 船坂陽子, 大塚洋平, 高山良子, 川名誠司, 佐伯秀久, 久保 亮治
    第114回日本皮膚科学会総会, May 2015, Japanese, 神奈川

  • Epidermis-specific ablation of claudin-1 in adult mice demonstrates a key role of tight junction barrier in the development of atopic dermatitis
    Kubo, A. Hirano, T. Kawasaki, H. Yokouchi, M. Atsugi, T. Amagai, M
    64th Meeting of Japanese Society of Allergology, May 2015, English, Tokyo, Japan

  • バリア破綻と皮膚炎がもたらす悪循環 〜アトピー性皮膚炎における経皮感作を考える〜
    久保 亮治
    第64回日本アレルギー学会学術大会, May 2015, Japanese, 東京

  • Tight junction barrier dysfunction induced by epidermis-specific claudin-1 ablation is sufficient to cause dermatitis in mice
    Kubo, A. Hirano, T. Yokouchi, M. Kawasaki, H. Atsugi, T. Amagai, M
    74th Annual Meeting of Society for Investigative Dermatology, May 2015, English, Atlanta, USA

  • Epidermolysis bullosa simplex with mottled pigmentationの２家系
    久保 亮治, 熊谷宜子, 芦田敦子, 常深祐一郎, 石河晃, 天谷雅行
    第377回日本皮膚科学会新潟地方会, Apr. 2015, Japanese, 新潟

  • 常にターンオーバーする表皮においてタイトジャンクションバリアの恒常性を維持するメカニズムの解析
    横内麻里子, 吉田和恵, 梶村眞弓, 末松誠, 天谷雅行, 久保 亮治
    第22回分子皮膚科学フォーラム, Apr. 2015, Japanese, 高知

  • 成体マウスにおける表皮特異的クローディン1欠損はタイトジャンクションバリアの漏洩と皮膚炎を引き起こす
    平野尚茂, 横内麻理子, 厚木徹, 天谷雅行, 久保 亮治
    第22回分子皮膚科学フォーラム, Apr. 2015, Japanese, 高知

  • SERPINB7遺伝子の変異を認めた長島型掌蹠角化症の１例
    幸絢子, 岡本真由美, 永田敬, 妹尾浩一, 塩濱愛子, 久保 亮治
    第136回日本皮膚科学会広島地方会, Mar. 2015, Japanese, 広島

  • 爪母上皮に著明な海綿状態を認めた
    崎山とも, 清水智子, 久保亮治, 海老原全, 齋藤昌孝
    第78回日本皮膚科学会東京支部学術大会, Feb. 2015, Japanese, 東京

  • 皮膚に表現型があらわれる先天性疾患の網羅的変異スクリーニングと新規原因遺伝子の探索
    久保 亮治, 新関寛徳
    厚生労働科研費班会議「小児科・産科領域疾患の大規模遺伝子解析ネットワークとエピゲノム解析拠点整備, Feb. 2015, Japanese, 東京

  • 糖尿病に合併しステロイド外用が著効したアミロイド苔癬の１例
    北原一博, 本多皓, 齋藤昌孝, 久保亮治, 大山学
    第859回日本皮膚科学会東京地方会（城西地区）, Jan. 2015, Japanese, 東京

  • Epidermis-specific ablation of claudin-1 in adult mice demonstrates the essential role of a tight junction barrier in skin homeostasis
    Hirano, T. Yokouchi, M. Atsugi, T. Amagai, M. Kubo, A
    The 39th Annual Meeting of the Japanese Society for Investigative Dermatology, Dec. 2014, English, Osaka, Japan

  • Tight junction barriers in the skin and skin diseases
    Kubo, A
    5th Pan Asian Pacific Skin Barrier Research Annual Symposium, Nov. 2014, English, Tainan

  • 長島型掌蹠角化症の一例
    中野敏明, 善家由香理, 西川沙織, 中村仁美, 新井達, 衛藤光, 三橋善比古, 久保 亮治
    第857回日本皮膚科学会東京地方会（城南地区）, Nov. 2014, Japanese, 東京

  • 9番染色体上のLMX1B遺伝子領域に染色体微小欠損を認めたNail-patella症候群の母娘例
    向井美穂, 安田文世, 伏間江貴之, 谷川瑛子, 天谷雅行, 久保 亮治
    第857回日本皮膚科学会東京地方会（城西地区）, Nov. 2014, Japanese, 東京

  • 自然発症性皮膚炎原因遺伝子Tmem79欠損マウスの確立と皮膚炎発症機構解析
    佐々木貴史, 塩濱愛子, 久保亮治, 天谷雅行
    厚生労働省科学研究費班会議『アトピー性皮膚炎発症機序の解明と皮膚バリアケアによる予防法の開発に関する研究, Nov. 2014, Japanese, 東京

  • 皮膚科領域における遺伝性疾患の診察・検査・診断の考え方
    久保 亮治
    第78回日本皮膚科学会東部支部学術大会, Oct. 2014, Japanese, 青森

  • 自然発症皮膚炎を起こすTmem79 KOマウスは層板顆粒の分泌異常を示す
    塩濱愛子, 佐々木貴史, 久保亮治, 川崎洋, 山田健人, 天谷雅行
    第42回日本臨床免疫学会総会, Sep. 2014, Japanese, 東京

  • フィラグリン欠損マウスの角層バリア機能破綻に対する乾燥環境因子の関与
    川崎洋, 久保亮治, 平野尚茂, 山田健人, 天谷雅行
    第42回日本臨床免疫学会総会, Sep. 2014, Japanese, 東京

  • A novel frameshift mutation of c.1638_1641delCAGT in KRT5 in a Japanese family with epidermolysis bullosa simplex with mottled pigmentation
    Kumagai, Y. Nakamura, Y. Sasaki, T. Takahashi, H. Amagai, M, Kubo, A
    3rd Eastern Asia Dermatology Congress, Sep. 2014, English, Jeju, Korea

  • Dowling-Meara型単純型表皮水疱症の1例
    田中博子, 吉田憲司, 根岸亜津佐, 石井健, 江藤宏夫, 佐々木貴史, 久保亮治, 石河晃
    第856回日本皮膚科学会東京支部合同臨床地方会（城南地区）, Sep. 2014, Japanese, 東京

  • 常染色体劣性遺伝のテネイシンX欠損によるエーラス・ダンロス症候群の1例
    崎山とも, 種本紗枝, 布袋祐子, 松本健一, 久保 亮治
    第855回日本皮膚科学会東京支部合同臨床地方会, Jul. 2014, Japanese, 東京

  • 片側性に序列性表皮母斑と掌蹠角化を認めたCostello症候群の体細胞モザイクの１例
    本多皓, 佐々木貴史, 中林一彦, 秦健一郎, 谷川瑛子, 久保 亮治
    第38回日本小児皮膚科学会学術大会, Jul. 2014, Japanese, 東京

  • 新規自然発症皮膚炎原因遺伝子Tmem79ノックアウトマウスの確立
    塩濱愛子, 佐々木貴史, 久保亮治, 川崎洋, 山田健人, 天谷雅行
    第35回日本炎症・再生医学会, Jul. 2014, Japanese, 沖縄

  • KRT5に新規遺伝子変異を認めた 色素異常型表皮水疱症の親子例
    熊谷宜子, 中村善雄, 佐々木貴史, 高橋勇人, 天谷雅行, 久保 亮治
    第854回日本皮膚科学会東京地方会（城西地区）, Jun. 2014, Japanese, 東京

  • アトルバスタチン／コレステロール液外用により皮疹を完治し得た両側性非典型CHILD症候群の一例
    久保 亮治, 天谷雅行
    第398回日本皮膚科学会北海道地方会, Jun. 2014, Japanese, 北海道

  • 長島型掌蹠角化症の原因遺伝子SERPINB7 の同定と患者30 例の変異解析
    久保 亮治, 塩濱愛子, 佐々木貴史, 中林一彦, 奥山虎之, 小崎健次郎, 工藤純, 秦健一郎, 梅澤明弘, 戸倉新樹, 石河晃, 新関寛徳, 椛島健治, 三橋善比古, 天谷雅行
    第113回日本皮膚科学会総会, May 2014, Japanese, 京都

  • Molecular Analysis of Biological Tissues using Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) and Gas Cluster Ion Beam (GCIB) sputtering
    Ishizaki, I. Miyayama, T. Sanada, N. Kubo, A. Setou, M
    The 16th Scientific International Symposium on SIMS (SISS16), May 2014, English, Sapporo

  • Tight junction barriers are functionally organized in hair follicles and sebaceous glands
    Atsugi, T. Yokouchi, M. Ohyama, M. Amagai, M. Kubo, A
    73th Annual Meeting Society for Investigative Dermatology, May 2014, English, Albuquerque, New Mexico

  • Mutations in SERPINB7, encoding a serine protease inhibitor, cause Nagashima-type palmoplantar keratosis
    Kubo, A. Shiohama, A. Sasaki, T. Nakabayashi, K. Kosaki, K. Kudoh, J. Hata, K. Umezawa, A. Tokura, Y. Ishiko, A. Niizeki, H. Kabashima, K. Mitsuhashi, Y. Amagai, M
    73th Annual Meeting Society for Investigative Dermatology, May 2014, English, Albuquerque, New Mexico

  • エクソーム解析による長島型掌蹠角化症の原因遺伝子SERPINB7の同定
    久保 亮治, 塩濱愛子, 佐々木貴史, 中林一彦, 川崎洋, 厚木徹, 清水厚志, 奥山虎之, 小崎健次郎, 工藤純, 秦健一郎, 梅澤明弘, 戸倉新樹, 石河晃, 新関寛徳, 椛島健治, 三橋善比古, 天谷雅行
    第21回分子皮膚科学フォーラム, Apr. 2014, Japanese

  • 新規自然発症皮膚炎原因遺伝子Tmem79の同定
    佐々木貴史, 塩濱愛子, 久保亮治, 川崎洋, 山本明美, 工藤純, 天谷雅行
    第21回分子皮膚科学フォーラム, Apr. 2014, Japanese, 京都

  • アトピー性皮膚炎と皮膚バリア
    久保亮治
    第77回日本皮膚科学会東京支部学術大会, Feb. 2014, Japanese, 東京, Domestic conference
    Keynote oral presentation

  • コネキシン26をコードするGJB2に変異を認めた難聴を伴う掌蹠角化症の１家系
    伏間江貴之, 本多皓, 佐々木貴史, 石戸谷淳一, 石河晃, 久保亮治
    第852回日本皮膚科学会東京支部東京地方会（城西地区）, Dec. 2013, Japanese, 東京, Domestic conference
    Oral presentation

  • Exacerbation of the skin barrier function of filaggrin-null mice in dry environment
    Kawasaki, H. Kubo, A. Hirano, T. Amagai, M
    42nd Annual Meeting of the Japanese Society for Immunology, Dec. 2013, English, Chiba, Japan, International conference
    Oral presentation

  • A homozygous nonsense mutation in Matted, a novel skin barrier gene associated with lamellar granule secretory system, causes spontaneous dermatitis in mice
    Sasaki, T. Shiohama, A. Kawasaki, H. Kubo, A. Yamada, T. Okano, H. Amagai, M
    42nd Annual Meeting of the Japanese Society for Immunology, Dec. 2013, English, Chiba, Japan, International conference
    Oral presentation

  • 新規自然発症皮膚炎原因遺伝子 matted の同定
    佐々木貴史, 塩濱愛子, 久保亮治, 川崎洋, 山本明美, 山田健人, 蜂矢隆久, 清水厚志, 岡野栄之, 工藤純, 天谷雅行
    第41回日本臨床免疫学会総会, Nov. 2013, Japanese, 下関, 山口, Domestic conference
    Oral presentation

  • 悪性黒色腫患者に生じた転移性病変との鑑別を要した二次性原発性悪性黒色腫の1例
    古市祐樹, 舩越建, 福田桂太郎, 久保亮治, 谷川瑛子, 森下加奈子, 木村佳史
    第851回日本皮膚科学会東京支部東京地方会（城西地区）, Nov. 2013, Japanese, 東京, Domestic conference
    Oral presentation

  • The Three Musketeers of the Epidermal Barrier
    Kubo, A
    4th Pan Asian Pacific Skin Barrier Research Annual Symposium, Oct. 2013, English, Okinawa, Japan, International conference
    Public discourse

  • TOF-SIMS Analysis of the Barrier Properties of the Three Layers of the Stratum Corneum to Metal Ions
    Ishizaki I, Hammond J, Kubo A, Kawasaki H, Nagao K, Ohashi Y, Amagai M, Kubo A
    15th European Conference on Applications of Surface and Interface Analysis, Oct. 2013, English, Italy, International conference
    Oral presentation

  • TOF-SIMS Imaging Unveiled the Stratum Corneum of the Skin Consisting of Three Layers with Distinct Properties
    Ishizaki, I. Hammond, J. Kubo, A. Kawasaki, H. Nagao, K. Ohashi, Y. Amagai, M. Kubo, A
    19th International Conference on Secondary Ion Mass Spectrometry, Oct. 2013, English, Italy, International conference
    Oral presentation

  • ロクロニウムによるアナフィラキシーショックの1例
    本田治樹, 安田文世, 福山雅大, 大方詩子, 藤尾由美, 舩越建, 永尾圭介, 岡本一真, 工藤樹彦, 四津良平, 久保亮治
    第850回日本皮膚科学会東京支部東京地方会（城西地区）, Sep. 2013, Japanese, 東京, Domestic conference
    Oral presentation

  • Molecular Barriology of the Stratum Corneum and Epidermal Tight Junctions
    Kubo, A
    International Symposium SFB 829 “Molecular Mechanism Regulating Skin Homeostasis 2013”, Sep. 2013, English, Cologne, Germany, International conference
    Public discourse

  • 角質層バリアと皮膚免疫
    久保亮治
    第29回日本皮膚悪性腫瘍学会学術大会, Aug. 2013, Japanese, 山梨, Domestic conference
    Invited oral presentation

  • NSDHL遺伝子変異を認めたCHILD症候群の一例
    吉田和恵, 野崎誠, 関敦仁, 守本倫子, 松岡健太郎, 佐々木貴史, 久保亮治, 海老原全, 渋谷紀子, 新関寛徳
    第37回日本小児皮膚科学会学術大会, Jul. 2013, Japanese, 東京, Domestic conference
    Oral presentation

  • 25年の経過を追えたKID症候群の1例
    角田梨沙, 池田政身, 加藤りか, 戸田郁子, 坪田一男, 大山学, 久保亮治
    第37回日本小児皮膚科学会学術大会, Jul. 2013, Japanese, 東京, Domestic conference
    Oral presentation

  • 新規自然発症皮膚炎原因遺伝子 matted の同定
    佐々木貴史, 塩濱愛子, 久保亮治, 川崎洋, 山本明美, 山田健人, 蜂矢隆久, 清水厚志, 岡野栄之, 工藤純, 天谷雅行
    第34回日本炎症・再生医学会, Jul. 2013, Japanese, 京都, Domestic conference
    Oral presentation

  • バリア異常からみたアトピー性皮膚炎の病態と治療
    Kubo Akiharu
    第112回日本皮膚科学会総会, Jun. 2013, Japanese, 横浜, Domestic conference
    Keynote oral presentation

  • 皮膚タイトジャンクションバリアから見た皮膚疾患の病態と病理
    Kubo Akiharu
    第102回日本病理学会総会, Jun. 2013, Japanese, 札幌, Domestic conference
    Keynote oral presentation

  • Filaggrin-null mice exhibit impaired stratum corneum barrier and enhanced percutaneous immune responses
    Kawasaki, H. Nagao, K. Kubo, A. Hata, T. Mizuno, H. Yamada, T. Amagai, M
    6th Asian Society for Pigment Cell Research(ASPCR) and Australasian Society of Dermatological Research(ASDR) congress 2013, May 2013, English, Sydney, Australia, International conference
    Oral presentation

  • The stratum corneum comprises three layers with distinct barrier properties to metal ions
    Kubo, A. Ishizaki, I. Kubo, A. Kawasaki, H. Nagao, K. Ohashi, Y. Amagai, M
    6th meeting of International Investigative Dermatology 2013, May 2013, English, Edinburgh, Scotland, International conference
    Oral presentation

  • A homozygous nonsense mutation of gene for Mattrin, a component of lamellar granule secretory system, produces spontaneous dermatitis in mice
    Sasaki, T. Shiohama, A. Kubo, A. Kawasaki, H. Ishida-Yamamoto, A. Yamada, T. Hachiya, T. Shimizu, A. Okano, H. Kudoh, J. Amagai, M
    The 6th meeting of International Investigative Dermatology 2013, May 2013, English, Edinburgh, Scotland, International conference
    Oral presentation

  • 経皮感作によるマウス気道の好酸球性炎症はフィラグリン欠損により遷延する
    鈴木雄介, 正木克宜, 加川志津子, 川崎洋, 永尾圭介, 久保亮治, 別役智子, 天谷雅行, 浅野浩一郎
    第53回日本呼吸器学会学術講演会, Apr. 2013, Japanese, 横浜, Domestic conference
    Oral presentation

  • バリア障害モデルマウスにおけるタイトジャンクションバリア機能についての検討
    横内麻里子, 川崎洋, 久保亮治, 天谷雅行
    第20回分子皮膚科学フォーラム, Apr. 2013, Japanese, 東京, Domestic conference
    Oral presentation

  • 皮膚表皮が持つバリア構造と機能からみた疾患治療戦略
    Kubo Akiharu
    日本薬学会 第133年会, Mar. 2013, Japanese, 横浜, Domestic conference
    Keynote oral presentation

  • Epicutaneous Sensitization In Filaggrin Gene-Depleted Mouse Induces Prolonged Airway Eosinophilia Without Obvious Dermatitis
    Suzuki, Y. Masaki, K. Kagawa, S. Kawasaki, H. Nagao, K. Kubo, A. Betsuyaku, T. Amagai, M. Asano, K
    2013 American Academy of Allergy, Asthma and Immunology Annual Meeting, San Antonio, Feb. 2013, English, Texas, USA, International conference
    Oral presentation

  • HSVの再活性化による口腔、食道潰瘍を呈した薬剤性過敏症症候群(DIHS)の1例
    森本亜里, 舩越建, 福島彩乃, 久保亮治, 海老原全, 林田哲, 真杉洋平, 亀山香織, 永尾圭介
    第76回日本皮膚科学会東京支部学術大会, Feb. 2013, Japanese, 東京, Domestic conference
    Oral presentation

  • 皮膚から全身へ 〜免疫・アレルギー感作に関わる皮膚表面のバリア機構〜
    Kubo Akiharu
    KOSE研究会, Feb. 2013, Japanese, 筑波, Domestic conference
    Others

  • アレルギー疾患発症因子としての皮膚バリア障害
    Kubo Akiharu
    第21回大分アレルギー講習会, Feb. 2013, Japanese, 東京, Domestic conference
    Others

  • 丘疹性ムチン沈着症の1例
    森下加奈子, 福田桂太郎, 久保亮治, 海老原全, 髙江雄二郎
    第847回日本皮膚科学会東京支部東京地方会, Jan. 2013, Japanese, 東京, Domestic conference
    Oral presentation

  • Imaging of the mammalian epidermis
    Kubo A
    The 37th Annual Meeting of the Japanese Society for Investigative Dermatology, Dec. 2012, English, Okinawa, Japan, International conference
    Public discourse

  • 経皮感作によるマウス気道の好酸球性炎症はフィラグリン欠損により遷延する
    鈴木雄介, 正木克宜, 加川志津子, 川崎洋, 永尾圭介, 久保亮治, 別役智子, 天谷雅行, 浅野浩一郎
    第62回日本アレルギー学会秋季学術大会, Nov. 2012, Japanese, 東京, Domestic conference
    Oral presentation

  • 経皮感作喘息マウスモデルの抗原感作時および暴露時におけるIL-23の役割
    正木克宜, 鈴木雄介, 加川志津子, 樹神元博, 小熊剛, 加畑宏樹, 宮田純, 田中希宇人, 川崎洋, 永尾圭介, 久保亮治, 福永興壱, 別役智子, 天谷雅行, 浅野浩一郎
    第62回日本アレルギー学会秋季学術大会, Nov. 2012, Japanese, 東京, Domestic conference
    Oral presentation

  • 〜免疫・アレルギー感作に関わる皮膚表面のバリア機構〜
    Kubo Akiharu
    第1回創薬イノベーション懇話会, Nov. 2012, Japanese, 東京, Domestic conference
    Others

  • Dendritic cells penetrate epidermal tight junction barriers to uptake external antigens: a possible involvement in atopic dermatitis
    Kubo A, Yoshida K, Yokouchi M, Ishii K, Kawasaki H, Ebihara T, Nagao K, Amagai M
    2012 Molecular Structure and Function of the Apical Junctional Complex in Epithelia and Endothelia, Oct. 2012, English, Kobe, Japan, International conference
    Oral presentation

  • The stratum corneum comprises three layers with distinct barrier properties, as revealed by TOF-SIMS imaging
    Kubo A, Ishizaki I, Kubo A, Kawasaki H, Ohashi Y, Amagai M
    61st Montagna Symposium on the Biology of Skin 2012, Portland, Oct. 2012, English, Oregon, USA, International conference
    Oral presentation

  • Cyclosporine A (CsA）内服にて症状が改善した皮下脂肪織炎様T細胞リンパ腫の1例
    藤尾由美, 髙江雄二郎, 野村尚志, 天谷雅行, 上田智基, 横山健次, 久保亮治
    第76回日本皮膚科学会東部支部学術大会, Sep. 2012, Japanese, 札幌, Domestic conference
    Oral presentation

  • トシリズマブ投与中の関節リウマチ患者の手背に生じた水疱性膿痂疹の1例
    笠井弘子, 土井亜希子, 種本紗枝, 松本奈央子, 吉田和恵, 久保亮治, 金子祐子, 竹内勤, 谷川瑛子
    第76回日本皮膚科学会東部支部学術大会, Sep. 2012, Japanese, 札幌, Domestic conference
    Oral presentation

  • フィラグリン欠損マウスにおける角層バリア機能異常と経皮免疫応答の亢進
    川崎洋, 永尾圭介, 久保亮治, 畑毅, 清水篤, 水野秀昭, 山田健人, 天谷雅行
    第40回日本臨床免疫学会総会, Sep. 2012, Japanese, 東京, Domestic conference
    Oral presentation

  • TOF-SIMSを用いた皮膚角質バリア構造の可視化
    Kubo Akiharu
    JST ERATO（末松ガスバイオロジープロジェクト）JSTさきがけ（炎症の慢性化機構の解明と制御）慶應義塾大学医学部医化学教室 共同講演会：質量分析で何が出来るか？ー生命科学研究での有用性ー, Sep. 2012, Japanese, 東京, Domestic conference
    Others

  • High-resolution TOF-SIMS Imaging reveals multi-layered barrier structure of the stratum corneum of skin
    Kubo A, Ishizaki I, Kubo A, Kawasaki H, Ohashi Y, Amagai M
    19th International Mass Spectrometry Conference, Sep. 2012, English, Kyoto, Japan, International conference
    Oral presentation

  • アレルギー疾患発症因子としての皮膚バリア障害
    Kubo Akiharu
    第49回小児アレルギー学会, Sep. 2012, Japanese, 大阪, Domestic conference
    Keynote oral presentation

  • Pros and Cons:バリア障害か炎症か：バリア障害か炎症か〜バリア障害について
    Kubo Akiharu
    第49回小児アレルギー学会, Sep. 2012, Japanese, 大阪, Domestic conference
    Keynote oral presentation

  • ヒト表皮におけるタイトジャンクションバリアの解析
    吉田和恵, 横内麻里子, 石井健, 永尾圭介, 天谷雅行, 久保亮治
    第39回皮膚かたち研究学会, Jul. 2012, Japanese, 東京, Domestic conference
    Oral presentation

  • 非Herlitz型接合部型表皮水疱症の1例
    笠井弘子, 松崎ひとみ, 吉岡寿朗, 永尾圭介, 天谷雅行, 石河晃, 久保亮治
    第36回日本小児皮膚科学会学術大会, Jul. 2012, Japanese, 前橋, Domestic conference
    Oral presentation

  • LIPH遺伝子変異を確認しえた先天性縮毛症/乏毛症の５例
    新関寛徳, 下村裕, 野崎誠, 重松由紀子, 開山麻美, 奥山虎之, 田久保国哉, 山本一哉, 道下崇史, 藤田英寿
    第36回日本小児皮膚科学会学術大会, Jul. 2012, Japanese, 前橋, Domestic conference
    Oral presentation

  • Molecular Barriology of the Skin ~Science of the Surface Barrier and Immunology~
    Kubo Akiharu
    エーザイ筑波研究所：研究会, Jun. 2012, Japanese, 筑波, Domestic conference
    Others

  • 間擦部に両側性の皮疹を呈し、NSDHL遺伝子に変異を認めCHILD症候群と考えた1例
    白樫祐介, 川崎洋, 松崎ひとみ, 海老原全, 佐々木りか子, 天谷雅行, 小崎健次郎, 久保亮治
    第111回日本皮膚科学会総会, Jun. 2012, Japanese, 京都, Domestic conference
    Oral presentation

  • Schwannomatosisの一例
    栗原佑一, 田中京子, 宮川俊一, 大久保匡
    第111回日本皮膚科学会総会, Jun. 2012, Japanese, 京都, Domestic conference
    Oral presentation

  • タイトジャンクションバリアと疾患
    久保亮治
    第111回日本皮膚科学会総会, Jun. 2012, Japanese, 京都, Domestic conference
    Invited oral presentation

  • 三次元イメージングで出会う皮膚銀河の天の川
    久保亮治
    第111回日本皮膚科学会総会, Jun. 2012, Japanese, 京都, Domestic conference
    Invited oral presentation

  • Mammalian skin-specific retroviral-like aspartic protease, SASPase is a key modulator of skin moisturization
    Matsui T, Miyamoto K, Kubo A, Kawasaki H, Ebihara T, Hata K, Ichinose S, Imoto I, Inazawa J, Kudoh J, Amagai M
    Joint Meeting of The 45th Annual Meeting of the Japanese Society of Developmental Biologists & The 64th Annual Meeting of the Japan Society for Cell Biology, May 2012, English, Kobe, Japan, International conference
    Oral presentation

  • Epicutaneous sensitization in filaggrin gene-depleted mouse induces prolonged airway eosinophilia and goblet cell hyperplasia without obvious dermatitis
    Suzuki Y, Masaki K, Kagawa S, Kawasaki H, Nagao K, Kubo A, Betsuyaku T, Amagai M, Asano K
    The American Thoracic Society’s 2012 International Conference, May 2012, English, San Francisco, California, USA,, International conference
    Oral presentation

  • Molecular Barriology of the Skin ~Unlock the Puzzle of Skin Barrier and Allergic Diseases~
    Kubo Akiharu
    Kanrinmaru Project Seminar 2012, May 2012, English, Tokyo, Japan, International conference
    Others

  • 皮膚バリア学 〜身体の内と外を区切るということ〜
    Kubo Akiharu
    大阪大学薬学部GCOEセミナー, Apr. 2012, Japanese, 大阪, Domestic conference
    Others

  • ィラグリン欠損マウスにおける角層バリア機能異常と経皮免疫応答の亢進
    川崎洋, 永尾圭介, 久保亮治, 畑毅, 清水篤, 水野秀昭, 山田健人, 天谷雅行
    第19回分子皮膚科学フォーラム, Apr. 2012, Japanese, 青森, Domestic conference
    Oral presentation

  • 長期にわたり経過を観察し得た劣性栄養障害型先天性表皮水疱症の1例
    Kubo Akiharu
    第53回日本皮膚科学会愛媛地方会橋本公二教授退職記念学術大会・総会, Mar. 2011, Japanese, 松山, Domestic conference
    Oral presentation

  • 皮膚バリア研究の新展開：タイトジャンクションバリアとランゲルハンス細胞の視点から
    Kubo Akiharu
    アトピー性皮膚炎治療研究会第16回シンポジウム, Feb. 2011, Japanese, 北九州, Domestic conference
    Oral presentation

  • Molecular Barriology of the Skin: Dynamic Interaction between Surface Physical Barriers and Immune System.
    Kubo Akiharu
    The 82th KEIO COEX meeting, Dec. 2010, English, Tokyo, Japan, International conference
    Oral presentation

  • 哺乳類皮膚バリア構造の解析〜物理的バリアと免疫細胞の相互作用を中心に〜
    Kubo Akiharu
    第33回日本分子生物学会年会・第83回日本生化学会大会合同大会, Dec. 2010, Japanese, 神戸, Domestic conference
    Oral presentation

  • 皮膚バリア機構の新しい捉え方（ステロイド・カルシニューリン阻害外用薬の使い方）
    Kubo Akiharu
    第60回日本アレルギー学会秋季学術大会, Nov. 2010, Japanese, 東京, Domestic conference
    Oral presentation

  • 全身電子線照射が著効した腫瘍期菌状息肉症の1例
    泉映里, 大内健嗣, 舩越建, 久保亮治, 谷川瑛子, 天谷雅行
    第833回日本皮膚科学会東京地方会, Nov. 2010, Japanese, 東京, Domestic conference
    Oral presentation

  • Epidermial tight junction barriers and trans-tight junction antigen uptake activity of Langerhans cells
    Kubo Akiharu
    第25回日本乾癬学会学術大会, Sep. 2010, Japanese, 山口, Domestic conference
    Oral presentation

  • 皮膚が隔てる外と内：皮膚バリア構造と免疫の視点から
    Kubo Akiharu
    第22回高遠シンポジウム, Aug. 2010, Japanese, 高遠, Domestic conference
    Oral presentation

  • 皮膚バリア機構の細胞生物学
    Kubo Akiharu
    皮膚基礎研究クラスターフォーラム第5回教育セミナー, Aug. 2010, Japanese, 東京, Domestic conference
    Oral presentation

  • 表皮タイトジャンクションバリアの生物学
    Kubo Akiharu
    第17回分子皮膚科学フォーラム, Jul. 2010, Japanese, 福岡, Domestic conference
    Oral presentation

  • 皮膚が隔てる外と内：皮膚バリア機構の細胞生物学
    Kubo Akiharu
    神奈川県皮膚科医会第133回例会・総会, Jul. 2010, Japanese, 横浜, Domestic conference
    Oral presentation

  • Langerhans cell dendrites penetrate through epidermal tight junction barrier during foreign antigen uptake
    Kubo Akiharu
    第62回日本細胞生物学会大会, May 2010, Japanese, 大阪, Domestic conference
    Oral presentation

  • Langerhans cell dendrites penetrate through epidermal tight junction barrier during foreign antigen uptake
    Kubo, A. Nagao, K. Yokouchi, M. Yoshida, K. Sasaki, H, Amagai,M
    70th Annual Meeting Society for Investigative Dermatology, May 2010, English, Atlanta, USA, International conference
    Oral presentation

  • 表皮ランゲルハンス細胞とタイトジャンクションバリアの協調による外来抗原取得機構
    Kubo Akiharu
    第19回東京免疫フォーラム, Feb. 2010, Japanese, 東京, Domestic conference
    Oral presentation

  • 進化からみた皮膚バリア：私たちは母なる海を身に纏う
    Kubo Akiharu
    2009年度日本皮膚科学会主催生涯教育セミナー, Feb. 2010, Japanese, 東京, Domestic conference
    Oral presentation

  • External antigen uptake by Langerhans cells through epidermal tight junction barriers
    Kubo,A Nagao, K, Yokouchi, M Sasaki, H, Amagai,M
    The 34th annual meeting of the Japanese society for investigative dermatology, Dec. 2009, English, Fukuoka,Japan, International conference
    Oral presentation

  • Filaggrin knockout mice as a tool for understandig the pathogenesis of atopic dermattis
    Kawasaki, H Kubo, A Nagao, K Hata, A Amagai,M
    The 39th Annual Meeting of the Japanese Society for Immunology, Dec. 2009, English, Osaka,Japan, International conference
    Oral presentation

  • アトピー性皮膚炎病態解明のためのフィラグリン欠失マウスの作製
    川崎洋, 久保亮治, 永尾圭介, 畑毅, 山田健人, 水野秀昭, 天谷雅行
    第16回分子皮膚科学フォーラム, Nov. 2009, Japanese, 札幌, Domestic conference
    Oral presentation

  • Activated Langerhans cells capture external antigens by sending their dendrites out through epidermal tight junctions
    Kubo,A Nagao, K, Yokouchi, M Sasaki, H, Amagai,M
    The 39th Annual Meeting of European Society for Dermatological Research (ESDR), Sep. 2009, English, Budapest, Hungary, International conference
    Oral presentation

  • イントロダクション：形態学的研究を通してみた繊毛・鞭毛研究の展開と展望
    Kubo Akiharu
    第61回日本細胞生物学会大会, Jun. 2009, Japanese, 名古屋, Domestic conference
    Oral presentation

  • Bowen病における中心体制御異常の検討
    久保亮治, 天谷雅行
    第108回日本皮膚科学会総会, Apr. 2009, Japanese, 福岡, Domestic conference
    Oral presentation

  • Sentan: A novel specific component of the apical structure of vertebrate motile cilia
    Kubo,A Yuba-Kubo, A Tsukita, S Tsukita, S Amagai,M
    The American Society for Cell Biology 48th Annual Meeting, Dec. 2008, English, San Francisco,U.S.A, International conference
    Oral presentation

  • アトピー性皮膚炎に関する最近のトピックス
    川崎洋, 久保亮治, 海老原全, 天谷雅行
    第4回TAP (Tokyo scientific forum for Atopic Dermatitis and Psoriasis）, Dec. 2008, Japanese, 東京, Domestic conference
    Oral presentation

  • Identification of novel ciliary proteins using microarray data of in vitro ciliogenesis
    Kubo, A, Tsukita, S
    46th Annual Meeting of the American Society for Cell Biology, Dec. 2008, English, San Diego, CA, USA, International conference
    Oral presentation

  • 繊毛先端に局在する新規蛋白sentanの同定
    久保亮治, 久保亜紀子, 月田承一郎, 月田早智子, 天谷雅行
    第15回分子皮膚科学フォーラム, Nov. 2008, Japanese, 京都, Domestic conference
    Oral presentation

  • Duhring疱疹状皮膚炎の一例
    Duhring疱疹状皮膚炎の一例
    第820回日本皮膚科学会東京地方会, Sep. 2008, Japanese, 東京, Domestic conference
    Oral presentation

  • Identification of novel ciliary proteins using microarray analyses of in vitro ciliogenesis
    Kubo, A Yuba-Kubo, A Amagai, M Tsukita, Sa Tsukita,Sh
    The 60th annual meeting of the Japan Society for cell biology, Jun. 2008, English, Yokohama,Japan, International conference
    Oral presentation

  • 繊毛形成時の遺伝子発現変化解析による新規繊毛構成蛋白の同定
    久保亮治, 久保亜紀子, 天谷雅行, 月田承一郎, 月田早智子
    第60回日本細胞生物学会, Jun. 2008, Japanese, 横浜, Domestic conference
    Oral presentation

  • Identification of novel ciliary proteins using microarray analyses of in vitro ciliogenesis
    Kubo, A Yuba-Kubo, A Amagai, M Tsukita, Sa Tsukita,Sh
    The International Investigative Dermatology 2008, May 2008, English, Kyoto,Japan, International conference
    Oral presentation

  • 急激な疼痛を伴う緊満性水疱により歩行困難を生じ、又ロゼット形成も認めた抗p200類天疱瘡の１例
    吉田哲也, 大内健嗣, 杉浦丹, 久保亮治, 天谷雅行, 大山文悟, 橋本隆, 堀口大輔
    第107回日本皮膚科学会総会学術大会, Apr. 2008, Japanese, 京都, Domestic conference
    Oral presentation

  • 急激な疼痛を伴う緊満性水疱により歩行困難を生じ、又ロゼット形成も認めた抗p200類天疱瘡の1例
    吉田哲也, 大内健嗣, 杉浦丹, 久保亮治, 天谷雅行, 大山文悟, 橋本隆, 堀口大輔
    第29回水疱症研究会, Oct. 2007, Japanese, 倉敷, Domestic conference
    Oral presentation

  • 細胞生物学におけるかたちへのこだわり
    Kubo Akiharu
    第71回日本皮膚科学会東部支部学術大会, Sep. 2007, Japanese, 札幌, Domestic conference
    Oral presentation

  • 特異な臨床を呈した環状肉芽腫の1例
    河野通良, 佐藤友隆, 久保亮治, 石河晃
    第812回日本皮膚科学会東京地方会, Jun. 2007, Japanese, 東京, Domestic conference
    Oral presentation

  • 免疫抑制状態患者の尋常性疣贅より生じたと考えられる有棘細胞癌の一例
    種瀬啓士, 秋好茜, 齋藤昌孝, 石河晃
    第23回日本皮膚悪性腫瘍学会学術大会, May 2007, Japanese, 新潟, Domestic conference
    Oral presentation

  • DDSが奏功したDuhring疱疹状皮膚炎および線状IgA水疱症の2例
    星野洋良, 大内結, 森布衣子, 木花いづみ, 久保亮治, 石河晃, 天谷雅行
    第106回日本皮膚科学会総会, Apr. 2007, Japanese, 横浜, Domestic conference
    Oral presentation

■ Affiliated Academic Society
  • Japanese Society for Immunology

  • Japan Society for Cell Biology

  • Society for Investigative Dermatology

  • The Japanese Society for Investigative Dermatology

  • Japanese Dermatological Association

■ Works
  • 広報活動「マルホラジオセミナー」
    久保亮治
    Mar. 2019
    子どものアトピー性皮膚炎 皮膚バリア機能とその異常

  • 慶應義塾医学部新聞「横内麻里子君（82回）平成29年日本皮膚科学会皆見省吾記念賞を受賞」
    久保亮治, 横内麻里子
    Sep. 2017

  • 日刊工業新聞「遺伝性の手足角質硬化症」
    Oct. 2013

  • マイナビニュース「慶応大など、原因不明の「長島型掌蹠角化症」の原因遺伝子異変を究明」
    久保亮治
    Oct. 2013

  • 日経電子版「慶大、皮膚の遺伝／長島型掌蹠角化症の原因遺伝子を同定」
    Oct. 2013

  • 日本の研究.com「慶應など、原因不明の「長島型掌蹠角化症」の原因遺伝子異変を究明」
    Oct. 2013

■ Research Themes
  • ヒト細胞競合モザイク疾患の疾患概念確立と病態解明
    久保 亮治
    日本学術振興会, 科学研究費助成事業, 学術変革領域研究(A), 神戸大学, 01 Apr. 2024 - 31 Mar. 2026

  • To understand the mechanism of cell competition/clonal expansion by understanding the pathogenesis of porokeratosis.
    久保 亮治, 福本 毅
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2023 - 31 Mar. 2026

  • Pathophysiology of porokeratosis and cell competition in human
    久保 亮治
    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), 01 Apr. 2020 - 31 Mar. 2023
    汗孔角化症とは、メバロン酸経路に関わる代謝酵素をコードする遺伝子の欠損により皮疹が生じる疾患である。汗孔角化症患者の2症例において、正常部と病変部のそれぞれから組織を採取し、初代培養ケラチノサイトを樹立した。いずれの細胞も、血清存在下では同じ増殖を示した。ところが無血清培地においては、正常皮膚由来のケラチノサイトは血清存在下と同様に増殖したのに対し、病変部皮膚由来のケラチノサイトは死滅した。無血清培地にコレステロールを添加したところ、病変部由来のケラチノサイトも正常に増殖したことから、患者病変部表皮の細胞ではメバロン酸経路が機能していないためにコレステロールの生合成ができず、正常に増殖できないことが考えられた。これら2種類の細胞間で生じる細胞競合現象を解析するために、2種類の細胞を単独培養した時には生じず、2種類の細胞を混合して培養した場合に生じる現象を探索する。2種類の細胞を適切な比率で混合し、正常細胞が変異細胞に取り込まれる条件と、逆に変異細胞が正常細胞に取り囲まれる培養条件においてmRNA発現を網羅的に比較した。変異細胞においては、コレステロール生合成経路の酵素のmRNA発現が上昇していた。2種類の細胞を混合培養した時に上昇すると予想される、細胞競合／細胞増殖に関わるシグナルについて検索中である。また、汗孔角化症の疾患モデルマウスを作成するため、汗孔角化症の原因遺伝子であるMVDとMVKについてfloxマウスを作成した。今後、K14-creERTマウスおよび組み換えが生じた場合に細胞が発する蛍光が変化するmT-mGマウスとの掛け合わせにより、適切な確立でcre-loxP組み換えが起こり、汗孔角化症の皮膚症状がタモキシフェン投与により誘導されるかを探索する。
    Competitive research funding

  • 細胞競合の概念に基づいた皮膚モザイク疾患の病態形成メカニズムの理解
    藤田 春美, 久保 亮治
    日本学術振興会, 科学研究費助成事業, 基盤研究(C), 慶應義塾大学, 01 Apr. 2020 - 31 Mar. 2021
    細胞競合とは、状態の異なる2種類の近接する細胞が環境への適応度で競合する現象であり、過去に主にショウジョウバエやマウスにおいて観察されてきた。これまでに申請者の所属研究室では、汗孔角化症の研究において、原因遺伝子に変異を持つケラチノサイトが正常ケラチノサイトと混ざり合う領域でのみ、過角化や炎症細胞浸潤などの病変が発生することを見出した。これより、ヒトの表皮において細胞競合現象が存在する可能性、および細胞競合現象が病変を誘発する原因となりうる可能性が強く示唆されている。 本研究は、変異ケラチノサイトが表皮内でクローン増殖することで発症する列序性表皮母斑・脂漏性角化症などの皮膚モザイク疾患群に着眼し、「変異遺伝子ごとの細胞競合現象の違いが、皮疹の形状や大きさの違いを生み出している」という仮説をたて、検討を行うものである。これまでの事業期間において、申請者は主に、変異ケラチノサイトと正常ケラチノサイトを用いたin vitro皮疹モデルの構築に携わり、実験手法を確立させた。これと並行して、培養細胞株を元にした疾患モデル細胞の準備も進めていたが、申請者の科研費指定機関ではない機関への転職による応募資格喪失により、本研究は今年度にて補助事業廃止となった。研究室においては今後も、他メンバーにより引き続き、本モデルを用いて正常・変異ケラチノサイト間で発生する細胞競合現象の分子メカニズムの検討が進められていく予定である。

  • 長島型掌蹠角化症の発症機序の解明
    久保亮治
    慶應義塾大学医学部学, 慶應義塾大学医学部学事振興資金, 01 Apr. 2019 - 31 Mar. 2020, Principal investigator
    Competitive research funding

  • CD1aを介した脂質抗原提示と皮膚炎惹起メカニズム
    梅垣知子
    文部科学省, 科学研究費補助金・基盤研究（Ｃ）, 01 Apr. 2018 - 31 Mar. 2020
    Competitive research funding

  • 長島型掌蹠角化症の病態解明と治療法開発
    久保亮治
    マルホ・高木皮膚科学振興財団, マルホ・高木賞, 2019 - 2020, Principal investigator
    Competitive research funding

  • 骨髄間葉系幹細胞動員活性に基づく表皮水疱症治療薬開発
    玉井克人
    国立研究開発法人 日本医療研究開発機構（AMED）, 橋渡し研究戦略的推進プログラム・シーズC, 01 Apr. 2017 - 31 Mar. 2019
    Competitive research funding

  • 長島型掌蹠角化症の変異未同定患者の変異探索と表皮菌叢情報に基づいた治療方法の確立
    塩濱愛子
    文部科学省, 科学研究費補助金・基盤研究（Ｃ）, 01 Apr. 2017 - 31 Mar. 2019
    Competitive research funding

  • Mechanism of Koebner phenomenon in CHILD syndrome
    Umegaki Noriko
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Keio University, 01 Apr. 2015 - 31 Mar. 2018
    CHILD syndrome is a genetic disorder associated with a mutation of the NSDHL gene. The patients with CHILD syndrome present scaly erythema with Koebner phenomenon, however the mechanism of the skin eruption has been unclear. In this study, we performed Gas Chromatography Mass Spectrometrythe (GC-MS) to analyze of the detailed cholesterol metabolites in CHILD syndrome and detected several unusual cholesterol metabolites in the affected skin. We also performed GC-MS using HaCaT cells treated by NSDHL inhibitor and detected identical unusual cholesterol metabolites, suggesting that our culture system could mimic the affected skin in CHILD syndrome in vitro.

  • Molecular mechanisms of the itch sensation and skin inflammation induced by epidermal tight junction barrier deficiency
    久保 亮治
    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Exploratory Research, Keio University, 01 Apr. 2015 - 31 Mar. 2017, Principal investigator
    The stratum corneum (SC) and tight junctions (TJs) form physical barriers in the skin. A congenital TJ barrier defect caused by a deficiency of claudin-1, which encodes a major epidermal TJ adhesion molecule, results in early neonatal death in mice and neonatal ichthyosis-sclerosing cholangitis syndrome in humans. These observations suggest the essential role of TJs in skin homeostasis. Here, we established tamoxifen (TAM)-inducible epidermis-specific claudin-1 knockout mice (K14-creERT+/-, Cldn1flox/flox mice) and investigated the pathophysiology of epidermal TJ defects in adult mice. To clarify the barrier defects of the SC and TJ separately, we measured water evaporation through isolated SC sheets (WETIS) ex vivo.On day 8, claudin-1 staining disappeared, but no elevation of WETIS was observed. On day 18, compact hyperkeratosis and increased WETIS were observed, suggesting that the TJ barrier leakage secondarily induced the SC barrier defect.
    Competitive research funding

  • Clarification of the pathogenesis of atopic disease by using filaggrin deficient mice in dry environment
    Kawasaki Hiroshi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Keio University, 01 Apr. 2014 - 31 Mar. 2017
    We aimed to clarify the pathogenesis that stratum corneum function of filaggrin deficient mice was exacerbated by the dry condition and lead to develop atopic disease, by using the filaggrin deficient mouse model grown in dry environment. Excessive barrier dysfunction and aberrant percutaneous sensitization were evident in the mice kept in dry condition, and these extents were more obvious in filaggrin deficient mice. Skin transcriptomic analysis of differentially expressed genes (DEG) between filaggrin deficient and wild-type mice revealed that very few genes were differentially expressed in normal humidity condition as compared with DEG in dry condition, suggesting that the impact of filaggrin deficiency was not significant in humid condition. Thus, we demonstrated that functional disorder due to filaggrin deficiency had an impact on phenotypic expression of the mice, closely associated with environmental factor of humidity.

  • The elucidation of the Nagashima-type palmoplantar keratosis caused by SERPINB7 protease inhibitor deficiency
    SHIOHAMA Aiko, MATSUI Takeshi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Keio University, 01 Apr. 2014 - 31 Mar. 2017
    Nagashima-type palmoplantar keratosis (NPPK) was an established autosomal recessive, early-onset palmoplantar keratoderma caused by mutations in the encoding SERPINB7 gene, a member of the serine protease inhibitor superfamily. To gain of more insight of NPPK, we promoted to create a knockout mouse model, selection of protease inhibited the activity of SERPINB7, and genome analysis of NPPK patients. We identified novel missense mutations of SERPINB7 gene with NPPK. The mutated proteins formed aggregates and mislocalized within corneocytes, possibly resulting in loss of protease inhibitory activity at the proper location. We applied to the haplotype analysis to determine whether the pathogenic mutations were derived from a common ancestor or represented mutations in the genomic region of SERPINB7. In consequence, the founder effect of the mutation and other recurrent mutations might explain why NPPK was so common in the Japanese population but not in Western populations.

  • Elucidation of the role of IL-23 in bronchial asthma caused by skin barrier dysfunction and drug discovery application
    Kagawa Shizuko, Fukunaga Koichi, Suzuki Yusuke, Kubo Akiharu, Kabata Hiroki, Masaki Katsunori, Mochimaru Takao, Matsusaka Masako
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Keio University, 01 Apr. 2014 - 31 Mar. 2017
    Th17 cells are the main cells that produce IL-17A.We found that IL-23 is required for the differentiation of Th17 cells via a patch application on the skin.In oder to find a therapeutic target of percutaneous sensitized asthma, I focused on the role of IL-23 produced in the local skin region and the role of Th17 in cytokine enhancement by administrating anti-IL-23 or control IgG to a percutaneously sensitized asthma mouse model, and then evaluating it for eosinophilic airway inflammation In the group to which the anti-IL-23 antibody was administered during the sensitization phase, the production of OVA-specific IgG1 antibody tended to decrease compared to the group to which the control IgG antibody was administered, and furthermore, the bronchoalveolar lavage fluid eosinophil count and eosinophil infiltration in tissues were found to decrease significantly.

  • Molecular mechanisms for the epidermal barrier homeostasis
    久保 亮治
    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Keio University, 01 Apr. 2014 - 31 Mar. 2017, Principal investigator
    In multicellular organisms, cells adopt various shapes, from flattened sheets of endothelium to dendritic neurons, that allow the cells to function effectively. Here, we elucidated the unique shape of cells in the stratified epithelia of the epidermis that allows them to achieve homeostasis of the tight junction (TJ) barrier. Using intimate in vivo 3D imaging, we found that the basic shape of TJ-bearing cells is a flattened Kelvin’s tetrakaidecahedron (f-TKD), an optimal shape for filling space. In vivo live imaging further elucidated the dynamic replacement of TJs on the edges of f-TKD cells that enables the TJ-bearing cells to translocate across the TJ barrier. We propose a spatiotemporal orchestration model of f-TKD cell turnover, where in the classic context of “form follows function,” cell shape provides a fundamental basis for the barrier homeostasis and physical strength of cornified stratified epithelia.
    Competitive research funding

  • ［難治性疾患等実用化研究事業 難治性疾患実用化研究事業］ 成人における未診断疾患に対する診断プログラムの開発に関する研究
    水澤英洋
    AMED（国立研究開発法人日本医療研究開発機構）, 2015 - 2017
    Competitive research funding

  • Induction of tolerance in the airways by extracellular ATP
    Suzuki Yusuke, KUBO Akiharu, KAWASAKI Hiroshi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Challenging Exploratory Research, 01 Apr. 2014 - 31 Mar. 2016
    Our animal experiments indicated amelioration of allergic airway inflammation after skin injury, which was opposite to commonsense. Thus we hypothesized that skin injury induced an allergy-protecting factor. We assumed the factor would be ATP and administrated ATP directly on animal skin. However, it turned out to be ineffective. We are seeking another candidate factor by analyzing injured skin tissue with DNA microarray.

  • Attempt to regenerate hair follicles using human iPS cell-derived epithelial and mesenchymal cells optimized for trichogenicity
    Ohyama Manabu, MASAYUKI AMAGAI, AKIHARU KUBO, HIDEYUKI OKANO
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), 01 Apr. 2013 - 31 Mar. 2016
    The aim of this study is to generate hair follicle structure using human induced pluripotent stem cell (iPSC)-derived epithelial and mesenchymal components optimized for trichogenicity. With regards to epithelial cells, a stable protocol to induce keratinocytes containing stem cell marker expressing cells was established. For trichogenic mesenchymal component preparation, an approach to generate multipotent mesenchymal stem cell-like cells was developed. The resultant cells are further programmed to acquire hair inductive property of dermal papilla cells. When co-grafted with normal human keratinocytes into immunedeficient mice, those cells gave rise to hair follicle-like structures with moderate reconstitution efficiency. However, regeneration of hair follicle structure exclusively consisted of human iPSC-derived cells is still technically very challenging, mainly because of relatively low efficiency and adjustment of the timing in the production of both iPSC-derived subsets.

  • ［挑戦的萌芽研究］ 15K15422 皮膚タイトジャンクションバリア破綻が誘発する痒みと皮膚炎発症の分子メカニズム解明
    久保亮治
    Grant-in-Aid for Scientific Research, 2015 - 2016, Principal investigator
    Competitive research funding

  • ［基盤研究 B］ 26293259 表皮バリアの形成・維持機構の解明とバリア構築に関わる新規因子の探索
    久保亮治
    Grant-in-Aid for Scientific Research, 2014 - 2016, Principal investigator
    Competitive research funding

  • Identification of novel atopic dermatitis candidate genes with sequencing analysis against skin barrier associated 200 genes.
    SASAKI Takashi, KUBO Akiharu
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Keio University, 01 Apr. 2012 - 31 Mar. 2015
    We established target resequencing method using next generation DNA sequencer for 600 Atopic Dermatitis (AD) related genes, and analyzed against Japanese AD patients. As a result, we isolated 6 candidate AD related mutations including natural immunity and signal pathway in epithelial cells. We analyzed the one candidate mutation against Japanese 150 AD patients among these candidates. Finally, we found the AD patients who show specific dermatitis at face and neck possess this mutation, frequently, and we currently are confirming this result with other Japanese AD patients.

  • ランゲルハンス細胞が誘導する経皮液性免応答の制御機構
    永尾 圭介, 久保 亮治, 山上 淳, 天谷 雅行, 舩越 建
    日本学術振興会, 科学研究費助成事業, 基盤研究(B), 慶應義塾大学, 01 Apr. 2012 - 31 Mar. 2015
    ランゲルハンス細胞(LC )による免疫制御機能を解析するため、表皮接着因子であるデスモグレイン3を中心とするいくつかのシステムを利用し、LCの機能解析を行った。昨年度までの研究で、LC は周囲ケラチノサイトからDsg3を獲得し、抗原提示を行うことがわかった。興味深いことに、LC は調節性T細胞をより優先的に増殖させることがわかり、自己抗原に対しては、免疫を抑制的に働かせることが示唆された。 本年度はこの解析をin vivoにて確認した。Dsg3を自己抗原とした自己免疫疾患モデルマウスを利用した。我々は以前Dsg3を自己抗原としたCD4陽性T細胞をクローニングし、Dsg３特異的CD4陽性T細胞受容体を遺伝子導入したマウスを確立した。このマウスの脾臓から採取したCD4陽性T細胞（Dsg3特異的）をRag2-/-マウスに移入することでマウスは皮膚炎を呈し、皮膚に浸潤したT細胞はケラチノサイトをアポトーシスに陥れる。この組織学的に見られる免疫応答は薬疹、SLEなどで見られる “interface dermatitis”の所見であり、我々はこのモデルをExperimental Autoimmune Dermatitis (EAD)と称している。このシステムは生理的な自己抗原に対する自己免疫モデルであり、T細胞が関与するメカニズムが詳細に解析された実験系である。LC欠損EADは通常EADと比較し、皮膚症状が増悪し、より多くのIFN-γもしくはIL-17産生CD4+ T細胞の浸潤が認められた。さらに、LC欠損EADでは制御性T細胞の減少が認められ、in vitroの実験と合致する所見を得た。これらの結果より、LCは制御性T細胞の誘導誘導を介して自己抗原に対する末梢性免疫寛容を誘導していることが考えられた。

  • ［慶應義塾・学事振興資金（共同研究)］ 外界・生体インターフェイスにおけるヘムオキシゲナーゼの生体防御・炎症制御機構解明
    久保亮治
    Keio Gijuku Academic Development Funds, 2014 - 2015, Principal investigator
    Competitive research funding

  • Clarification of the molecular and cellular mechanisms of central and peripheral tolerance to pemphigus autoantigen
    AMAGAI Masayuki, NAGAO Keisuke, KUBO Akiharu
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (S), Keio University, 11 May 2009 - 31 Mar. 2014
    The purpose of this study is to clarify the pathogenic roles of T cells specific for desmoglein 3 (Dsg3), the autoimmune target antigen in pemphigus vulgaris, and the mechanisms of tolerance to Dsg3 in vivo. Dsg3-specific T cells were able to induce not only pemphigus vulgaris, but also unexpectedly interface dermatitis and psoriasis-like skin lesions. This model provides an important tool to dissect the pathophysiological mechanisms for interface dermatitis as experimental autoimmune dermatitis (EAD). While Dsg3-specific T cells are usually deleted in the thymus (central tolerance), it was demonstrated that these T cells could be deleted solely in the periphery (peripheral tolerance) when thymic epithelial cells did not express Dsg3. Further dissection of the mechanisms for peripheral tolerance will lead us to develop a novel therapeutic strategy for antigen-specific immune suppression.

  • ［挑戦的萌芽研究］ 25670507 アトピー性皮膚炎における皮膚タイトジャンクションバリア破綻の病的意義の解明
    久保亮治
    Grant-in-Aid for Scientific Research, 2013 - 2014, Principal investigator
    Competitive research funding

  • ［基盤研究 A］ 22249044 ランゲルハンス細胞と表皮タイトジャンクションによる動的表皮免疫バリア機構の解析
    久保亮治
    Grant-in-Aid for Scientific Research, 2010 - 2013, Principal investigator
    Competitive research funding

  • ［挑戦的萌芽研究］ 23659555 TOF-SIMS（飛行時間型質量分析）顕微鏡を用いた角質バリア機能可視化法の開発
    久保亮治
    Grant-in-Aid for Scientific Research, 2011 - 2012, Principal investigator
    Competitive research funding

  • ［慶應義塾・咸臨丸プロジェクト］ 皮膚”バリオロジー”：バリア機能異常から見たアレルギー疾患病態解明
    久保亮治
    慶應義塾・咸臨丸プロジェクト, 2008 - 2012, Principal investigator
    Competitive research funding

  • Development of new objective methods to assess disease activity in pemphigus using monoclonal single-chain- variable-fragment antibodies
    ISHII Ken
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Keio University, 2008 - 2010
    In order to develop new objective methods to assess the disease activity in pemphigus, we performed the detailed characterization of repertories of monoclonal anti-desmoglein (Dsg) 1 autoantibodies isolated from a pemphigus foliaceus patient by phage display. Major epitopes on desmoglein bound by autoantibodies in many pemphigus patients were uncovered. The reactivity against the epitopes by pemphigus sera correlates with the disease activity. These findings will facilitate the development of new objective methods to assess the disease activity in pemphigus patients.

  • The analysis of centrosome replication cycle in Bowen's disease
    KUBO Akiharu, ISHII Ken, AMAGAI Masayuki
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Keio University, 2008 - 2009
    Centrosome consists of mother and daughter centrioles and pericentriolar materials. Centrosome duplicates only once per cell cycle and the duplication cycle is strictly regulated. In many cancer cells, the centrosomal cycle is dysregulated, which induces multi-polar spindles or cytokinesis failure and aneuploidy. In this study, we established a specific antibody against daughter centrioles and succeeded to count the number of mother and daughter centrioles per cell in the biopsy specimens of Bowen's disease and squamous cell carcinoma. Centrosome duplication cycle was dysregulated and multiple centrioles were observed in so-called "clumping cells" of Bowen's disease. In clumping cells, the number of mother and daughter centrioles are almost same, which indicated that cytokinesis failure causes the formation of "clumping cells". We found that Aurora-A kinase was overexpressed in "clumping cells". So we established transgenic mice that overexpress Aurora-A kinase specifically in the epidermis. In these mice, binuclear cells were found in the basal layer of epidermis, suggesting that Aurora-A overexpression is associated with the pathogenesis of Bowen's disease.

  • Molecular mechanisms of cell-cell adhesion in cancer cells
    FURUSE Mikio, TSUKITA Sachiko, ADACHI Makoto, KUBO Akiharu, TAMURA Atsushi, ODA Yukako, SASAKI Hiroyuki
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research on Priority Areas, 2005 - 2009
    The tight junction is one of the characteristic structures in epithelial cells, from which cancer is derived, and works as a barrier to restrict the free diffusion of solutes through the intercellular space. In this study, we investigated the molecular structure and function of tight junctions. We found that the artificial modification of the barrier property of tight junctions accelerates growth of intestinal epithelial cells and results in enlargement of the intestine. We also clarified for the first time the molecular constituents of tricellular contacts.

  • 繊毛形成における中心子複製機構および繊毛形成機構の解析
    久保 亮治
    日本学術振興会, 科学研究費助成事業, 若手研究(B), 慶應義塾大学, 2006 - 2007
    In vitro で繊毛形成を誘導した時の繊毛上皮における遺伝子発現の変化を網羅的に解析する事で、繊毛形成および中心体複製の制御に関わる因子の探索を行った。繊毛上皮の発生過程における種々のタイミングで特徴的な遺伝子発現パターンを示す遺伝子を複数単離し、中心体とcentriolar satellitesの双方に局在する新規蛋白と、繊毛の先端に局在する新規蛋白について解析を進めた。 1)新規蛋白p110は繊毛細胞および精子に特異的に発現し、繊毛を持つ単細胞生物から哺乳類まで幅広く保存されている蛋白であった。 p100はcentriolar satellitesを構成するPCM-1蛋白と直接結合しcentriolar satellitesに局在するだけでなく、基底小体のproximal側にも存在する事を示した。また、p100の過剰発現によりcentriolar satellitesがdisassembleされる事を示した。これらの結果はp110が繊毛形成に必須の蛋白である事を強く示唆している。 2)新規蛋白sentanが繊毛の先端に局在する事を示した。繊毛のaxonemeを構成する微小管のうち外側の微小管はdoublet構造を取っているが、先端付近ではB tubuleが先に終止し、A tubuleのsingletが先端まで伸びて、central微小管と結合している。免疫電顕によりsentan蛋白がsinglet A tubuleと細胞膜を繋ぐ構造に局在する事を示した。また、sentan蛋白が細胞膜脂質成分のうちphosphatidylserineと特異的に結合する事を示した。これまで、繊毛の先端構造を作る蛋白は全く同定されておらず、sentanが初めて同定された蛋白となる。

  • 新規非膜系オルガネラcentriolar satellitesの構造・機能解析
    久保 亮治
    日本学術振興会, 科学研究費助成事業, 若手研究(B), 京都大学, 2004 - 2005
    これまでに、centriolar satellitesが微小管上をダイニンにより運動し中心体周辺に集積する新規非膜系オルガネラである事、中心体の複製・成熟にcentriolar satellitesが必要であることを明らかにしてきた。また、繊毛細胞に於ける中心子複製および繊毛形成時に重要な役割を果たすとされてきたfibrous granulesと呼ばれる未知の構造物がcentriolar satellitesと同一のオルガネラであることを示してきた。今回の研究ではまず、centriolar satellites構成蛋白であるPCM-1のドメイン解析を行い、PCM-1同士のhomophilicな結合に必要な部位を二ヶ所同定した。同定した部位を元にしてPCM-1同士の結合を特異的に阻害するペプチドを作成した。PCM-1同士の結合を阻害すると、centriolar satellitesが観察できなくなった。現在までに得られた他の知見と合わせて、PCM-1蛋白がcentriolar satellitesのscattered proteinであると結論づけられた。 一方、繊毛上皮におけるcilia形成においてcentriolar satellitesが果たす役割を解析するために、マウス気管上皮細胞を用いて、繊毛上皮のprimary cultureの系を確立し、既知の中心体関連蛋白質の繊毛上皮形成の過程における発現変化、局在変化について詳細に解析した。また、繊毛上皮形成過程における遺伝子発現変化をGene chipを用いて網羅的に解析する事で、centriolar satellitesと中心体の双方に局在する新規蛋白を単離した。現在この新規蛋白について解析を進めている。

  • Claudins in the epithelium/endothelium barrier dysfucrition
    TSUKITA Shoichiro, FURUSE Mikio, KUBO Akiharu, ADACHI Makoto
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (A), KYOTO UNIVERSITY, 2002 - 2004
    In multicellular organisms, the internal environment must be isolated and buffered against the external environment, and further divided into various compositionally distinct fluid compartments. This compartmentalization is established by cellular sheets of epithelia delineating the body surface and cavities. For epithelial cellular sheets to function as barriers, there must be some seal to the diffusion of solutes through the paracellular pathway. Tight junctions(TJs) have teen shown to be responsible for this intercellular sealing in vertebrates. Recent identification of claudins, cell adhesion molecules responsible for the TJ barrier, opened a new way to perturb individual compartments, and to evaluate the physiological relevance of each compartment at a whole body level. To date, 24 members of the claudin family have been identified in human/mouse, and these are reported to be expressed in individual cell layers in various combinations and mixing ratios. It has been shown that a particular compartment can be destroyed, when the gene for major species of claudins constituting TJs of its delineating epithelial cell layer is homozygously knocked out in mice. In this project, we generated and reported claudin-1-and claudin-5-deflcient mice. Claudin-1 is expressed in large amounts in the epidermis, and claudin-1-deficient mice showed severe dysfunction of the epidermal barrier, being dehydrated quickly after birth. Endothelial cells of brain blood vessels primarily express claudin-5, and in claudin-5-deficient mice, the blood-brain barrier was severely affected. Now we can discuss the relationship of claudins with the compartmentalization in vertebrates.

  • Molecular mechanism for cell-cell adhesion in canceration and metastasis
    TSUKITA Shoichiro, FURUSE Mikio, KUBO Akiharu, ADACHI Makoto, TSUKITA Sachiko
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research on Priority Areas, KYOTO UNIVERSITY, 2000 - 2004
    More than 90% of malignant tumors are derived from the epithelium. Thus, in this project, we focused on the analyses of tight junctions and ERM proteins to clarify the nature of the. epithelium. Major results are as follows: 1. Claudin-1-deficient mice were generated. Their epidermal barrier was affected, and the proliferation of epidermal cells appeared to be abnormal. 2. Claudin-5-deficient mice were generated. Their blood-brain barrier was affected in a size-dependent manner. This finding was intriguing from the viewpoint of drug deliver to the brain tumors. 3. The dynamic behavior of claudin-based tight junction strands was successfully observed in live cells. Their behavior was more dynamic than ever expected. 4. Snail, a transcription factor, plays a key role in the epithelial-mesenchymal transition, which is important in the metastasis of cancer cells. We found that Snail completely repressed the transcription of occludin and claudins through its direct binding to the E-boxes of the promoter regions of these genes. 5. Claudin-1 was shown to be overexpressed in human colon cancer (in collaboration with Prof. Nakamura's group). 6. We established the system, in which a certain gene can be double-knocked out in cultured epithelial cells. With this system, an epithelial cell line lacking the expression of ZO-1 and ZO-2 was established. 7. The structure of the gene product of NF2, an ERM-like tumor suppressor gene, was clarified by X-ray diffraction analyses (in collaboration with Prof.Hakozaki's group).

  • 新規非膜系オルガネラcentriolar satellitesの構造・機能解析
    久保 亮治
    日本学術振興会, 科学研究費助成事業, 若手研究(B), 京都大学, 2002 - 2003
    1.PCM-1のドミナントネガティブ変異体によるcentriolar satellitesの機能・構造解析 PCM-1蛋白はcentriolar satellitesのscaffold proteinであることをこれまでの研究で示してきた。今回PCM-1蛋白同士の結合を担う部位を同定した。このPCM-1同士の結合を担う部分のペプチドを細胞に高発現させるとcentriolar satellitesを分解する事ができた。このペプチドによりendogenousなPCM-1同士の結合が阻害される事でcentriolar satellitesが分解すると考えられる。Centriolar satellitesが分解された細胞はPCM-1をRNAiによりknock-downした細胞とほぼ同じphenotype(中心体のpericentrin量の減少、細胞周期停止)を示した。これらの結果から、PCM-1蛋白がcentriolar satellitesという構造を取ることが、その機能発現に必須であることが示された。 2.ツーハイブリ法によるPCM-1結合蛋白の探索 PCM-1蛋白の各ドメインをbaitとしてツーハイブリ法を行い、PCM-1結合蛋白を探索した。いくつかのcandidateについて、タグをつけて細胞に発現させ、その局在を検討した。また、可能性のあるものについて抗体を作成し、細胞内局在およびPCM-1との結合を検討中である。

  • Regulation of the tight junction barrier by synthetic peptides: Towards the development of a new drug delivery method
    FURUSE Mikio, KUBO Akiharu
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), KYOTO UNIVERSITY, 2001 - 2002
    The blood-brain barrier (BBB) is thought to protect the brain from various harmful materials circulating in the blood. On the other hand, BBB prevents many potential drugs from entering the central nervous system (CNS). Many researchers have therefore tried to loosen the BBB for therapeutic purposes in various CNS disorders, but limited information on the molecular basis for BBB has hampered these trials. To establishment of the BBB, well-developed tight junctions (TJs) between adjacent endothelial cells are indispensable, in addition to various transporters in their plasma membranes. Recently, claudin-5 was identified as a major TJ cell adhesion molecule in brain endothelial cells. Here we show that in claudin-5-deficient mice, BBB is loosened in a size-selective manner. In the brain of these mice, the morphology/development of blood vessels was not altered, and TJs consisting of claudin-12 remained in the endothelial cells. Tracer experiments and magnetic resonance imaging revealed that in the claudin-5-deficient brain, the BBB against small molecules (<800 Da), but not larger molecules, was selectively affected. These findings not only provide new insight into the basic molecular physiology of BBB but also improve drug delivery methods.

■ Industrial Property Rights
  • 慢性皮膚炎の治療のための医薬組成物
    久保亮治, 久保亜紀子, 荒尾知子, 天谷雅行, 末松誠
    特願2018-193755, 12 Oct. 2018, 学校法人慶應義塾
    Patent right

  • 自然発症皮膚炎の新規原因因子及び皮膚疾患モデル動物
    Masayuki Amagai, Takashi, Sasaki Jun, Kudou, Akiharu Kubo
    特願2012-047521, 05 Mar. 2012, 学校法人慶應義塾, 特開2013-179920, 12 Sep. 2013, 特許第5959235号, 01 Jul. 2016
    Patent right

  • アレルギー疾患モデル動物
    Masayuki Amagai, Akiharu Kubo
    特願2010-511897, 15 May 2009, 学校法人慶應義塾, WO2009/139191, 19 Nov. 2009, 特許第5606907号, 05 Sep. 2014
    Patent right

  • Allergic Disease Model Animals
    Masayuki Amagai, Akiharu Kubo
    PCT/JP2009/002161, 15 May 2009, Keio University, WO2009/139191, 19 Nov. 2009, US 8350118, 08 Jan. 2013
    Patent right

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