Research activity information

• 2015 文部科学大臣表彰若手科学者賞


• 2006 大阪大学, 山村賞

• Control of mucociliary clearance in airway host defense

  Noriko Shinjyo, Masahiko Shigemura, Yasutaka Okabe

  Abstract Respiratory infections remain a major threat to global health. To counter these insults, the respiratory system has evolved multilayered defense strategies that integrate anatomical and mechanical barriers with both innate and adaptive immune responses. Mucociliary clearance (MCC) serves as a cornerstone of airway host defense, whereby coordinated ciliary beating at the luminal surface of the airway epithelium drives the efficient removal of inhaled particles and pathogens. This process provides robust, broad-spectrum protection against both routine environmental exposures and emerging respiratory pathogens. In this review, we summarize the current understanding of respiratory barrier function and defense strategies, with a particular emphasis on the immunological and metabolic mechanisms that regulate MCC. We further highlight the role of aldehyde dehydrogenases in preventing ciliary damage and preserving MCC function, thereby conferring protection against environmental stress and respiratory infections.

  Oxford University Press (OUP), Jul. 2026, International Immunology

  [Refereed][Invited]

  Scientific journal


• Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure

  Noriko Shinjyo, Haruna Kimura, Tomomi Yoshihara, Jun Suzuki, Masaya Yamaguchi, Shigetada Kawabata, Yasutaka Okabe

  Corresponding, American Society for Clinical Investigation, May 2025, Journal of Clinical Investigation, 135(14) (14), English, No password

  [Refereed]

  Scientific journal

  添付ファイルのURL


• Targeted labeling and depletion of alveolar macrophages using VeDTR mouse technology

  Yuki Nakayama, Miwa Sasai, Ayumi Kuratani, Masaaki Okamoto, Daisuke Okuzaki, Kentaro Yamamoto, Chikako Ono, Masaya Yamaguchi, Shigetada Kawabata, Noriko Shinjyo, Yasutaka Okabe, Yoshiharu Matsuura, Manabu Ato, Masahiro Yamamoto

  Elsevier BV, Mar. 2025, iScience, 28(3) (3), 111975 - 111975

  [Refereed]

  Scientific journal


• Development and organization of omental milky spots

  Yasutaka Okabe

  Jul. 2024, Immunological Reviews

  [Refereed][Invited]

  Scientific journal


• Aberrant RNA sensing in regulatory T cells causes systemic autoimmunity

  Domnica Luca, Sumin Lee, Keiji Hirota, Yasutaka Okabe, Junji Uehori, Kazushi Izawa, Anna-Lisa Lanz, Verena Schütte, Burcu Sivri, Yuta Tsukamoto, Fabian Hauck, Rayk Behrendt, Axel Roers, Takashi Fujita, Ryuta Nishikomori, Min Ae Lee-Kirsch, Hiroki Kato

  Chronic and aberrant nucleic acid sensing causes type I IFN–driven autoimmune diseases, designated type I interferonopathies. We found a significant reduction of regulatory T cells (T _regs ) in patients with type I interferonopathies caused by mutations in ADAR1 or IFIH1 (encoding MDA5). We analyzed the underlying mechanisms using murine models and found that T _reg -specific deletion of Adar1 caused peripheral T _reg loss and scurfy -like lethal autoimmune disorders. Similarly, knock-in mice with T _reg -specific expression of an MDA5 gain-of-function mutant caused apoptosis of peripheral T _regs and severe autoimmunity. Moreover, the impact of ADAR1 deficiency on T _regs is multifaceted, involving both MDA5 and PKR sensing. Together, our results highlight the dysregulation of T _reg homeostasis by intrinsic aberrant RNA sensing as a potential determinant for type I interferonopathies.

  American Association for the Advancement of Science (AAAS), Mar. 2024, Science Advances, 10(9) (9)

  [Refereed]

  Scientific journal


• Aldh1a2 + fibroblastic reticular cells regulate lymphocyte recruitment in omental milky spots

  Tomomi Yoshihara, Yasutaka Okabe

  Lymphoid clusters in visceral adipose tissue omentum, known as milky spots, play a central role in the immunological defense in the abdomen. Milky spots exhibit hybrid nature between secondary lymph organs and ectopic lymphoid tissues, yet their development and maturation mechanisms are poorly understood. Here, we identified a subset of fibroblastic reticular cells (FRCs) that are uniquely present in omental milky spots. These FRCs were characterized by the expression of retinoic acid–converting enzyme, Aldh1a2, and endothelial cell marker, Tie2, in addition to canonical FRC-associated genes. Diphtheria toxin–mediated ablation of Aldh1a2+ FRCs resulted in the alteration in milky spot structure with a significant reduction in size and cellularity. Mechanistically, Aldh1a2+ FRCs regulated the display of chemokine CXCL12 on high endothelial venules (HEVs), which recruit blood-borne lymphocytes from circulation. We further found that Aldh1a2+ FRCs are required for the maintenance of peritoneal lymphocyte composition. These results illustrate the homeostatic roles of FRCs in the formation of non-classical lymphoid tissues.

  Rockefeller University Press, Feb. 2023, Journal of Experimental Medicine, 220(5) (5), No password

  [Refereed]

  Scientific journal

  添付ファイルのURL


• Immune Niche Within the Peritoneal Cavity.

  Yasutaka Okabe

  There are numbers of leukocytes present in peritoneal cavity, not only protecting body cavity from infection but also contributing to peripheral immunity including natural antibody production in circulation. The peritoneal leukocytes compose unique immune compartment, the functions of which cannot be replaced by other lymphoid organs. Atypical lymphoid clusters, called "milky spots", that are located in visceral adipose tissue omentum have the privilege of immune niche in terms of differentiation, recruitment, and activation of peritoneal immunity, yet mechanisms underlying the regulation are underexplored. In this review, I discuss the emerging views of peritoneal immune system in the contexts of its development, organization, and functions.

  Springer International Publishing, Jan. 2021, Current topics in microbiology and immunology, 123 - 134

  [Refereed][Invited]

  Scientific journal


• Introduction: Special Issue-The Origins of Macrophages and Their Roles Beyond Immunology

  Yasutaka Okabe

  Nov. 2018, International immunology, 30(11) (11), 483 - 484, English

  [Invited]


• Molecular control of the identity of tissue-resident macrophages.

  Yasutaka Okabe

  Macrophages are present in virtually almost all tissues, exhibiting highly heterogeneous phenotypes as a consequence of adaptation to local tissue environments. Tissue-resident macrophages perform specialized functions that are essential for the maintenance of tissue homeostasis, and abnormalities of their functions are linked to various pathologies. Recent advances have shown that tissue-specific transcriptional programs are responsible for functional specialization of macrophages in different tissues. Here, I discuss the molecular basis of tissue-resident macrophage specialization and how it is regulated by tissue environmental cues.

  Oct. 2018, International immunology, English

  [Refereed][Invited]

  Scientific journal


• Wormhole Travel for Macrophages

  Yasutaka Okabe, Ruslan Medzhitov

  Apr. 2016, CELL, 165(3) (3), 518 - 519, English

  [Refereed][Invited]

  Scientific journal

  添付ファイルのURL


• Tissue biology perspective on macrophages

  Yasutaka Okabe, Ruslan Medzhitov

  Lead, Jan. 2016, NATURE IMMUNOLOGY, 17(1) (1), 9 - 17, English, No password

  [Refereed]

  Scientific journal

  添付ファイルのURL


• How the immune system spots tumors

  Yasutaka Okabe, Ruslan Medzhitov

  Lead, Sep. 2014, ELIFE, 3(e04476) (e04476), e04476, English, No password

  [Invited]

  Scientific journal

  添付ファイルのURL


• Tissue-Specific Signals Control Reversible Program of Localization and Functional Polarization of Macrophages

  Yasutaka Okabe, Ruslan Medzhitov

  Lead, May 2014, CELL, 157(4) (4), 832 - 844, English, No password

  [Refereed]

  Scientific journal

  添付ファイルのURL


• Regulation of the innate immune response by threonine-phosphatase of Eyes absent

  Yasutaka Okabe, Teruyuki Sano, Shigekazu Nagata

  Lead, Jul. 2009, NATURE, 460(7254) (7254), 520 - U99, English

  [Refereed]

  Scientific journal


• IFN regulatory factor (IRF) 3/7-dependent and -independent gene induction by mammalian DNA that escapes degradation

  Yasutaka Okabe, Kohki Kawane, Shigekazu Nagata

  Lead, Nov. 2008, EUROPEAN JOURNAL OF IMMUNOLOGY, 38(11) (11), 3150 - 3158, English

  [Refereed]

  Scientific journal


• Opposite effects of Rho family GTPases on engulfment of apoptotic cells by macrophages

  M Nakaya, M Tanaka, Y Okabe, R Hanayama, S Nagata

  Mar. 2006, JOURNAL OF BIOLOGICAL CHEMISTRY, 281(13) (13), 8836 - 8842, English

  [Refereed]

  Scientific journal


• Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation

  Y Okabe, K Kawane, S Akira, T Taniguchi, S Nagata

  Lead, Nov. 2005, JOURNAL OF EXPERIMENTAL MEDICINE, 202(10) (10), 1333 - 1339, English

  [Refereed]

  Scientific journal


• Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA

  H Yoshida, Y Okabe, K Kawane, H Fukuyama, S Nagata

  Lead, Jan. 2005, NATURE IMMUNOLOGY, 6(1) (1), 49 - 56, English

  [Refereed]

  Scientific journal


• X-ray crystal structure of IRF-3 and its functional implications

  K Takahasi, NN Suzuki, M Horiuchi, M Mori, W Suhara, Y Okabe, Y Fukuhara, H Terasawa, S Akira, T Fujita, F Inagaki

  Nov. 2003, NATURE STRUCTURAL BIOLOGY, 10(11) (11), 922 - 927, English

  [Refereed]

  Scientific journal


• Induction of IRF‐3/‐7 kinase and NF‐κB in response to double‐stranded RNA and virus infection: common and unique pathways

  Tomokatsu Iwamura, Mitsutoshi Yoneyama, Kazumi Yamaguchi, Wakako Suhara, Wakana Mori, Kazutaka Shiota, Yasutaka Okabe, Hideo Namiki, Takashi Fujita

  Background

  Infection by virus or treatment with double-stranded RNA (dsRNA) results in the activation of transcription factors including IRF-3, IRF-7 and a pleiotropic regulator NF-kappaB by specific phosphorylation. These factors are important in triggering a cascade of antiviral responses. A protein kinase that is yet to be identified is responsible for the activation of these factors and plays a key role in the responses.

  Results

  The signal cascade was analysed using sensitive assays for the activation of IRF-3 and NF-kappaB, and various inhibitors. We found that the activation of IRF-3 and NF-kappaB by dsRNA or virus involves a process that is sensitive to Geldanamycin. Although the induction of NF-kappaB by dsRNA/virus and TNF-alpha involves common downstream pathways including IKK activation, the upstream, Geldanamycin-sensitive process was unique to the dsRNA/virus-induced signal. By an in vitro assay using cell extract, we found an inducible protein kinase activity with physiological specificity of IRF-3 phosphorylation. Furthermore, the same extract specifically phosphorylated IRF-7 in a similar manner.

  Conclusions

  Double-stranded RNA or virus triggers a specific signal cascade that results in the activation of the IRF-3/-7 kinase we detected, which corresponds to the long-sought signalling machinery that is responsible for triggering the early phase of innate response. The signal branches to a common NF-kappaB activation cascade, thus resulting in the activation of a set of critical transcription factors for the response.

  Apr. 2001, Genes to Cells, 6, 375-388., English

  [Refereed]

  Scientific journal


• PACT, a Double-Stranded RNA Binding Protein Acts as a Positive Regulator for Type I Interferon Gene Induced by Newcastle Disease Virus

  Tomokatsu Iwamura, Mitsutoshi Yoneyama, Nobuo Koizumi, Yasutaka Okabe, Hideo Namiki, Charles E. Samuel, Takashi Fujita

  Virus infection triggers innate responses to host cells including production of type I interferon (IFN). Since IFN production is also induced by treatment with poly(I:C), viral double-stranded (ds) RNA has been postulated to play a direct role in the process. In the present study, we investigated the effect of dsRNA binding proteins on virus-induced activation of the IFN-beta gene. We found that PACT, originally identified as protein activator for dsRNA-dependent protein kinase (PKR) and implicated in the regulation of translation, augmented IFN-beta gene activation induced by Newcastle disease virus. Concomitantly with the augmented activity of IFN-beta enhancer, increased activity of NF-kappaB and IRF-3 and IRF-7 was observed. For the observed effect, the dsRNA-binding activity of PACT was essential. We identified residues of PACT that interact with a presumptive target molecule to exert its function. Furthermore, PACT colocalized with viral replication complex in the infected cells. Thus the observed effect of PACT is novel and PACT is involved in the regulation of viral replication and results in a marked increase of cellular IFN-beta gene expression.

  Mar. 2001, Biochemical and Biophysical Research Communications, 282, 515-523., English

  [Refereed]

  Scientific journal

• マクロファージを標的とした創薬の可能性

  岡部泰賢

  Aug. 2023, BIO Ex-xpress


• マクロファージ マクロファージと組織微小環境

  岡部泰賢

  11 Apr. 2016, JSI Newsl, 24(2) (2), 17, Japanese


• Eyes absentのスレオニン脱リン酸化酵素活性による自然免疫活性化の調節機構

  佐野晃之, 岡部泰賢, 長田重一

  25 Sep. 2009, 生化学, ROMBUNNO.1S1A-7, Japanese


• 【免疫研究最前線 2007】自然免疫応答の制御 自己のDNAによる自然免疫の活性化

  岡部 泰賢, 長田 重一

  (株)羊土社, Dec. 2006, 実験医学, 24(20) (20), 3161 - 3167, Japanese


• DNase IIノックアウトマウス胎仔におけるIFN‐βの致死作用

  吉田英行, 岡部泰賢, 川根公樹, 長田重一

  05 Nov. 2004, 日本免疫学会総会・学術集会記録, 34, 242, Japanese

• 大網リンパ組織の発生機構

  Single work, 臨床免疫・アレルギー科, Oct. 2023


• 臨床免疫・アレルギー科

  小原和樹, 岡部泰賢

  Joint work, 組織マクロファージによる恒常性維持のメカニズム, 科学評論社, Jul. 2023


• 炎症と免疫

  新庄記子, 岡部泰賢

  Contributor, 組織マクロファージ, 先端医学社, Apr. 2021


• 細胞

  岡部泰賢

  Contributor, 組織マクロファージの遺伝子発現制御, ニューサイエンス社, Dec. 2018


• メディカル・サイエンス・ダイジェスト

  岡部 泰賢

  Contributor, 組織常在性マクロファージ, ニューサイエンス社, Jul. 2018


• 医学のあゆみ 自然免疫の最前線

  岡部 泰賢

  Contributor, 組織マクロファージの分化と機能, 医歯薬出版株式会社, Jun. 2018


• 炎症と免疫

  岡部 泰賢

  Contributor, 腹腔マクロファージ～機能と発生の分子基盤～, 先端医学社, May 2018


• 医学のあゆみ マクロファージのすべて

  岡部 泰賢

  Contributor, 腹腔マクロファージ研究の進歩, 医歯薬出版株式会社, Oct. 2016


• 実験医学増刊 サイトカインによる免疫制御と疾患

  岡部 泰賢

  Contributor, スレオニン脱リン酸化酵素Eyaによる自然免疫の制御, 羊土社, Aug. 2010


• 実験医学増刊 免疫研究最前線2007

  岡部 泰賢

  Contributor, 自己のDNAによる自然免疫の活性化, 羊土社, Dec. 2006

• 反応性アルデヒドを基盤とする気道繊毛障害

  第53回日本毒性学会学術年会, Jul. 2026, Japanese

  [Invited]

  Invited oral presentation


• Tissue-Resident Macrophages in the Regulation of Immune Niches

  Yasutaka Okabe

  第54回日本免疫学会, Dec. 2025, English

  [Invited]

  Invited oral presentation


• Tissue-Resident Macrophages in the Regulation of Immune Niches

  Yasutaka Okabe

  Yonsei University, College of Life Science and Biotechnology, Nov. 2025, English

  [Invited]

  Invited oral presentation


• Tissue-Resident Macrophages in the Regulation of Immune Niches

  Yasutaka Okabe

  Yonsei University, College of Medicine, Nov. 2025, English

  [Invited]

  Invited oral presentation


• The role of mucociliary clearance in airway host defense

  Yasutaka Okabe

  第14回IFReC国際シンポジウム, Nov. 2024, English

  [Invited]

  Invited oral presentation


• Role of retinoic acid in the formation of non-classical lymphoid tissues

  Academia Sinica, Taipei-Taiwan, Mar. 2024, English

  [Invited]

  Invited oral presentation


• Non-classical lymphoid organ formation in body cavity

  Yasutaka Okabe

  第100回日本生理学会, Mar. 2023, English

  [Invited]

  Invited oral presentation


• Macrophage Plasticity in Homeostasis and Diseases

  Yasutaka Okabe

  第83回日本血液学会学術集会, Sep. 2021

  [Invited]


• Regulation of Body Cavity Immunity

  Yasutaka Okabe

  The 73rd Annual Meeting of the Japan Society for Cell Biology, Jun. 2021

  [Invited]


• 組織マクロファージの生物学

  岡部泰賢

  神戸大学医学研究科シグナル伝達医学研究展開センターセミナー, Aug. 2019

  [Invited]


• 免疫の『場』としての脂肪組織

  岡部泰賢

  第40回 日本炎症・再生医学会, Jul. 2019

  [Invited]


• ビタミンA依存的な腫瘍関連肺胞マクロファージの活性化

  岡部 泰賢

  京王プラザホテル, Jul. 2018, Japanese

  [Invited]


• 組織マクロファージの生物学

  岡部 泰賢

  京都大学医学部, Mar. 2018, Japanese

  [Invited]


• マクロファージから考える糖尿病 - マクロファージと組織微小環境 -

  岡部 泰賢

  富山大学 医学部, Mar. 2018, Japanese

  [Invited]


• マクロファージの組織発生

  岡部 泰賢

  北海道大学遺伝子病制御研究所, Mar. 2018, Japanese

  [Invited]


• 生体恒常性と組織マクロファージ

  岡部 泰賢

  東京大学先端科学技術研究センター, Feb. 2018, Japanese

  [Invited]


• Functional Specialization of Macrophages in Peripheral Tissues

  Yasutaka Okabe

  The 46th Annual Meeting of The Japanese Society for Immunology, Dec. 2017, English

  [Invited]

  Invited oral presentation


• Recent Advances in Macrophage Biology

  Yasutaka Okabe

  The 46th Annual Meeting of The Japanese Society for Immunology, Dec. 2017, Japanese

  [Invited]

  Invited oral presentation


• Tissue macrophage identity

  Yasutaka Okabe

  24th East Asia Joint Symposium on Biomedical Research, Oct. 2017, English

  [Invited]


• 組織マクロファージの発生機構

  岡部 泰賢

  第19回免疫サマースクール2017 in 湘南, Aug. 2017, Japanese

  [Invited]


• Tissue macrophage identity

  Yasutaka Okabe

  The 44th Annual Meeting of the Japanese Society for Immunolgy, Nov. 2015, English, International conference

  [Invited]

  Invited oral presentation


• Tissue-derived signals in the control of macrophage identities

  Yasutaka Okabe

  Japanese Association of Cancer Immunotherapy & Japanese Society of Molecular Cell Biology of Macrophages, Jul. 2014, English, International conference

  [Invited]

  Invited oral presentation

• 敗血症に立脚した体腔リンパ組織の生体防御応答の解明

  岡部 泰賢, 鈴木 淳

  日本学術振興会, 科学研究費助成事業, 基盤研究(B), 大阪大学, Apr. 2025 - Mar. 2028, Principal investigator


• 粘液繊毛クリアランスを基盤としたユニバーサル呼吸器感染予防法の創生

  鈴木淳

  Feb. 2026 - Dec. 2027, Principal investigator


• The roles of pleural adipose tissue-derived factors in the regulation of innate B-cell niche and airway immune responses

  新庄 記子, 岡部 泰賢

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Osaka University, Apr. 2022 - Mar. 2027, Coinvestigator


• 新規中皮細胞が制御する体腔免疫系

  岡部 泰賢

  日本学術振興会, 科学研究費助成事業, 挑戦的研究(萌芽), Jun. 2019 - Mar. 2023, Principal investigator

  前年度までの解析により我々が同定した中皮細胞が体腔への白血球移動を制御する知見を得た。今年度はその分子メカニズムを明らかにするため、大網組織のシングルセルRNA-seq解析を行った結果、大網組織を構成する支持細胞が５つのクラスターに分類されることを見出し、そのうちの１つのクラスターが本研究で着目する中皮細胞に相当することをトランスクリプトーム解析により見出した。実際、ジフテリア毒素投与依存的に中皮細胞を除去したマウス大網ではそのクラスターが選択的に除去されることから、このクラスターが我々の見出した中皮細胞種を含む細胞集団であることを結論した。一方、ジフテリア毒素投与依存的に中皮細胞種を除去すると血管内皮細胞におけるいくつかのケモカイン産生が顕著に低下することを今年度新たに見出した。それらケモカインの機能を阻害すると白血球のリクルートメントが抑制されることから、中皮細胞と血管内皮細胞の機能的な相互作用が体腔への白血球リクルートメントを制御する可能性が示唆された。


• Molecular basis for tissue macrophage diversity

  Okabe Yasutaka

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Apr. 2019 - Mar. 2022, Principal investigator

  Tissue-resident macrophages are a highly heterogeneous population performing specialized functions that are essential for the maintenance of tissue homeostasis. In this study, we focused on the transcription factors that are uniquely expressed in specific tissue-resident macrophage subsets, and determined whether these transcription factors function as master regulators controlling tissue-specific functions of macrophages. We found that the expression of some of these transcription factors exhibits variation among macrophages present in the same tissue environments. Additionally, we observed the fluctuation of the expression of the transcription factors results in the difference in the global gene expression pattern between tissue macrophages.


• Heterogeneousな組織境界層を起点とした時空間的な細胞間相互作用

  岡部 泰賢

  科学技術振興機構, 戦略的な研究開発の推進 戦略的創造研究推進事業 さきがけ, 京都大学, 2019 - 2022, Principal investigator

  組織とはいわば区画化された空間であり、物理的な境界により細胞社会が隔離されることが独立した多細胞システムとして機能するために必要不可欠です。一方、境界は物質や細胞を選択的に通過させることで外界や組織間とのコミュニケーションを制御する動的な場でもあります。本研究では内臓表面で境界を形成する中皮層に着目し、組織境界層を起点とした細胞間相互作用の新たな様式を提唱します。


• ビタミンA依存的な腫瘍関連肺胞マクロファージの活性化

  岡部泰賢

  喫煙科学財団, 一般研究, Apr. 2017 - Mar. 2020, Principal investigator


• 組織マクロファージの多様性制御機構の解明

  岡部泰賢

  かなえ医薬振興財団, 研究助成, Apr. 2018 - Mar. 2019, Principal investigator


• マクロファージと組織実質細胞の相互作用

  岡部泰賢

  清水免疫学・神経科学振興財団, 助成, Apr. 2018 - Mar. 2019, Principal investigator


• 脂肪組織における常在性マクロファージの生理的機能

  岡部泰賢

  アステラス病態代謝研究会, 研究助成, Apr. 2018 - Mar. 2019


• 脂肪代謝制御における上皮増殖因子受容体陽性マクロファージの機能

  岡部泰賢

  武田科学振興財団, 医学系研究奨励, Apr. 2018 - Mar. 2019, Principal investigator


• 組織マクロファージの表現型多様性機構の解明

  岡部泰賢

  日本免疫学会, 免疫学若手研究者自立支援 きぼうプロジェクト, 2016 - 2019, Principal investigator


• Mechanisms of tissue macrophage development

  OKABE Yasutaka

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research), Kyoto University, 2016 - 2019

  Macrophages are one of the most multifunctional cell types performing important roles in development, host defense, homeostasis, and tissue repair. They are present in virtually every tissue and display diverse phenotypes depending on their anatomical locations where they perform specialized functions that are essential for normal tissue physiology and homeostasis. Additionally, a variety of diseases are associated with the disruption of tissue-specific macrophage functions. Aberrant macrophage functions contribute to a broad spectrum of pathologies including cancer, metabolic diseases, atherosclerosis, asthma, inflammatory bowel disease, rheumatoid arthritis, and fibrosis. Thus, uncovering the specialized functions of tissue macrophages is critical for the understanding of normal tissue functions as well as for therapeutic implication for human diseases. We have identified novel mesothelial cell type which regulate the development and the functional specialization of macrophages in body cavity.


• 組織マクロファージの表現型多様性機構の解明

  岡部泰賢

  三菱財団, 自然科学研究助成, 2017 - 2018, Principal investigator


• 造血及びアポトーシスにおける染色体DNA分解の生理作用

  岡部 泰賢

  日本学術振興会, 科学研究費助成事業, 特別研究員奨励費, 大阪大学, 2004 - 2005

  アポトーシスの過程では死細胞の染色体DNAが積極的に分解される。このDNA分解には死細胞内で作用するDNase(CAD,caspase-activated DNase)と、死細胞を貪した後、マクロファージで作用するDNaseIIが関与している。これまでの研究の過程で、DNaseIIを欠損するマウスではマクロファージが未分解のDNAを大量に蓄積すること、そしてIFNbを初めとする自然免疫系が構成的に活性化され、その作用によりマウスは胎生期に死滅することを示した。 本年度は、DNAを分解できず蓄積するDNaseII欠損マクロファージにおいて、IFNb、CXCL10、TNFa遺伝子が特異的に活性化されている事を明らかにした。また、DNaseII欠損マウスから調製したマクロファージやmouse embryonic fibroblast(MEF)にアポトーシス細胞を貪食させるとこれらの遺伝子が活性化されたことから、リソソームでの分解を逃れたDNAが自然免疫系を活性化することを示した。ところで、Toll-like receptor(TLR)はバクテリアDNAやウイルスRNAを認識し、自然免疫系を活性化する事が知られている。DNaseII欠損マウスと種々のTLR欠損マウスやそのアダプター因子の欠損マウスを交配することにより自己の未分解のDNAがTLRの機構を活性化している可能性を検討したが、このシグナルはTLR非依存的であった。 以上の知見により、自己DNAの分解機構の破錠がバクテリアDNAやウイルスRNAによるシグナルとは異なる経路で自然免疫系を活性化することが明らかとなった。

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