Research activity information

• Mar. 2020 理化学研究所, 桜舞賞


• Nov. 2015 第44回日本免疫学会学術集会, Best Presentation Award


• Jun. 2014 Molecular Cell Biology of Macrophages (MMCB) 2014, Young Investigator Award


• Aug. 2013 理化学研究所, Noyori Prize


• Aug. 2012 理化学研究所, Biology Prize


• Nov. 2009 第8回次世代を担う若手ファーマ・バイオフォーラム 2009, 優秀発表者賞

• Deep-sea water preserves depth-dependent water molecular network signatures after recovery

  Takaharu Sasaki, Yoko Osafune, Wakana Yoshida, Alexander Stoilov, Shogo Shigeoka, Tamae Takada, Kayoko Okuzako, Roumiana Tsenkova

  Lead, May 2026, ChemRxiv, English

  Scientific journal


• RelB and C/EBPα critically regulate the development of Peyer's patch mononuclear phagocytes.

  Takashi Kanaya, Toshi Jinnohara, Sayuri Sakakibara, Naoko Tachibana, Takaharu Sasaki, Tamotsu Kato, Marc Riemann, Jianshi Jin, Katsuyuki Shiroguchi, Eiryo Kawakami, Hiroshi Ohno

  To establish protection against harmful foreign antigens, the small intestine harbors guardian sites called Peyer's patches (PPs). PPs take up antigens through microfold (M) cells and transfer them to the sub-epithelial dome (SED), which contains a high density of mononuclear phagocytes (MPs), for T cell-priming. Accumulating evidence indicates that SED-MPs have unique functions other than T cell-priming to facilitate mucosal immune responses; however, the crucial factors regulating the functions of SED-MPs have not been determined. Here we performed transcriptome analysis, and identified the gene signatures of SED-MPs. Further data interpretation with transcription factor (TF) enrichment analysis estimated TFs responsible for the functions of SED-MPs. Among them, we found that RelB and C/EBPα were preferentially activated in SED-MPs. RelB-deficiency silenced the expression of IL-22BP and S100A4 by SED-MPs. On the other hand, C/EBPα-deficiency decreased the expression of lysozyme by SED-MPs, resulting the increased invasion of orally administered pathogenic bacteria into PPs and mesenteric lymph nodes. Our findings thus demonstrate that RelB and C/EBPα are essential to regulate the functions of SED-MPs.

  Oct. 2024, Mucosal immunology, English, International magazine

  [Refereed]

  Scientific journal


• Food antigens suppress small intestinal tumorigenesis.

  Takaharu Sasaki, Yuna Ota, Yui Takikawa, Tommy Terrooatea, Takashi Kanaya, Masumi Takahashi, Naoko Taguchi-Atarashi, Naoko Tachibana, Haruka Yabukami, Charles D Surh, Aki Minoda, Kwang Soon Kim, Hiroshi Ohno

  Food components suppressing small intestinal tumorigenesis are not well-defined partly because of the rarity of this tumor type compared to colorectal tumors. Using Apcmin/+ mice, a mouse model for intestinal tumorigenesis, and antigen-free diet, we report here that food antigens serve this function in the small intestine. By depleting Peyer's patches (PPs), immune inductive sites in the small intestine, we found that PPs have a role in the suppression of small intestinal tumors and are important for the induction of small intestinal T cells by food antigens. On the follicle-associated epithelium (FAE) of PPs, microfold (M) cells pass food antigens from lumen to the dendritic cells to induce T cells. Single-cell RNA-seq (scRNA-seq) analysis of immune cells in PPs revealed a significant impact of food antigens on the induction of the PP T cells and the antigen presentation capacity of dendritic cells. These data demonstrate the role of food antigens in the suppression of small intestinal tumorigenesis by PP-mediated immune cell induction.

  Sep. 2024, Frontiers in immunology, 15, 1373766 - 1373766, English, International magazine

  [Refereed]

  Scientific journal


• Fatty acid overproduction by gut commensal microbiota exacerbates obesity.

  Tadashi Takeuchi, Keishi Kameyama, Eiji Miyauchi, Yumiko Nakanishi, Takashi Kanaya, Takayoshi Fujii, Tamotsu Kato, Takaharu Sasaki, Naoko Tachibana, Hiroki Negishi, Misato Matsui, Hiroshi Ohno

  Although recent studies have highlighted the impact of gut microbes on the progression of obesity and its comorbidities, it is not fully understood how these microbes promote these disorders, especially in terms of the role of microbial metabolites. Here, we report that Fusimonas intestini, a commensal species of the family Lachnospiraceae, is highly colonized in both humans and mice with obesity and hyperglycemia, produces long-chain fatty acids such as elaidate, and consequently facilitates diet-induced obesity. High fat intake altered the expression of microbial genes involved in lipid production, such as the fatty acid metabolism regulator fadR. Monocolonization with a FadR-overexpressing Escherichia coli exacerbated the metabolic phenotypes, suggesting that the change in bacterial lipid metabolism is causally involved in disease progression. Mechanistically, the microbe-derived fatty acids impaired intestinal epithelial integrity to promote metabolic endotoxemia. Our study thus provides a mechanistic linkage between gut commensals and obesity through the overproduction of microbe-derived lipids.

  Feb. 2023, Cell metabolism, 35(2) (2), 361 - 375, English, International magazine

  [Refereed]

  Scientific journal


• RIPK1 blocks T cell senescence mediated by RIPK3 and caspase-8.

  Takayuki Imanishi, Midori Unno, Natsumi Yoneda, Yasutaka Motomura, Miho Mochizuki, Takaharu Sasaki, Manolis Pasparakis, Takashi Saito

  Receptor-interacting protein kinase 1 (RIPK1) regulates cell death and inflammation. Here, we show that T cell-specific RIPK1 deficiency in mice leads to the premature senescence of T cells and induces various age-related diseases, resulting in premature death. RIPK1 deficiency causes higher basal activation of mTORC1 (mechanistic target of rapamycin complex 1) that drives enhanced cytokine production, induction of senescence-related genes, and increased activation of caspase-3/7, which are restored by inhibition of mTORC1. Critically, normal aged T cells exhibit similar phenotypes and responses. Mechanistically, a combined deficiency of RIPK3 and caspase-8 inhibition restores the impaired proliferative responses; the elevated activation of Akt, mTORC1, extracellular signal-regulated kinase, and caspase-3/7; and the increased expression of senescence-related genes in RIPK1-deficient CD4 T cells. Last, we revealed that the senescent phenotype of RIPK1-deficient and aged CD4 T cells is restored in the normal tissue environment. Thus, we have clarified the function of RIPK3 and caspase-8 in inducing CD4 T cell senescence, which is modulated by environmental signals.

  Jan. 2023, Science advances, 9(4) (4), eadd6097, English, International magazine

  [Refereed]

  Scientific journal


• Role of leukotriene B4 (LTB4)-LTB4 receptor 1 signaling in post-incisional nociceptive sensitization and local inflammation in mice.

  Miho Asahara, Nobuko Ito, Yoko Hoshino, Takaharu Sasaki, Takehiko Yokomizo, Motonao Nakamura, Takao Shimizu, Yoshitsugu Yamada

  Leukotriene B4 (LTB4) is a potent lipid mediator involved in the recruitment and activation of neutrophils, which is an important feature of tissue injury and inflammation. The biological effects of LTB4 are primarily mediated through the high-affinity LTB4 receptor, BLT1. Postoperative incisional pain is characterized by persistent acute pain at the site of tissue injury and is associated with local inflammation. Here, we compared the role of LTB4-BLT1 signaling in postoperative incisional pain between BLT1-knockout (BLT1KO) and wild-type (BLT1WT) mice. A planter incision model was developed, and mechanical pain hypersensitivity was determined using the von Frey test before and after incision. Local infiltration of neutrophils and inflammatory monocytes was quantified by flow cytometry. Inflammatory cytokine levels in the incised tissue were also determined. Mechanical pain hypersensitivity was significantly reduced in BLT1KO mice compared to BLT1WT mice at 2, 3, and 4 days after incision. LTB4 levels in the tissue at the incision site peaked 3 hours after the incision. Infiltrated neutrophils peaked 1 day after the incision in both BLT1KO and BLT1WT mice. The accumulation of inflammatory monocytes increased 1-3 days after the incision and was significantly more reduced in BLT1KO mice than in BLT1WT mice. In BLT1KO mice, Interleukin-1β and Tumor Necrosis Factor-α levels 1 day after the incision were significantly lower than those of BLT1WT mice. Our data suggest that LTB4 is produced and activates its receptor BLT1 in the very early phase of tissue injury, and that LTB4-BLT1 signaling exacerbates pain responses by promoting local infiltration of inflammatory monocytes and cytokine production. Thus, LTB4-BLT1 signaling is a potential target for therapeutic intervention of acute and persistent pain induced by tissue injury.

  2022, PloS one, 17(10) (10), e0276135, English, International magazine

  [Refereed]

  Scientific journal


• Acetate differentially regulates IgA reactivity to commensal bacteria.

  Tadashi Takeuchi, Eiji Miyauchi, Takashi Kanaya, Tamotsu Kato, Yumiko Nakanishi, Takashi Watanabe, Toshimori Kitami, Takashi Taida, Takaharu Sasaki, Hiroki Negishi, Shu Shimamoto, Akinobu Matsuyama, Ikuo Kimura, Ifor R Williams, Osamu Ohara, Hiroshi Ohno

  The balance between bacterial colonization and its containment in the intestine is indispensable for the symbiotic relationship between humans and their bacteria. One component to maintain homeostasis at the mucosal surfaces is immunoglobulin A (IgA), the most abundant immunoglobulin in mammals1,2. Several studies have revealed important characteristics of poly-reactive IgA3,4, which is produced naturally without commensal bacteria. Considering the dynamic changes within the gut environment, however, it remains uncertain how the commensal-reactive IgA pool is shaped and how such IgA affects the microbial community. Here we show that acetate-one of the major gut microbial metabolites-not only increases the production of IgA in the colon, but also alters the capacity of the IgA pool to bind to specific microorganisms including Enterobacterales. Induction of commensal-reactive IgA and changes in the IgA repertoire by acetate were observed in mice monocolonized with Escherichia coli, which belongs to Enterobacterales, but not with the major commensal Bacteroides thetaiotaomicron, which suggests that acetate directs selective IgA binding to certain microorganisms. Mechanistically, acetate orchestrated the interactions between epithelial and immune cells, induced microbially stimulated CD4 T cells to support T-cell-dependent IgA production and, as a consequence, altered the localization of these bacteria within the colon. Collectively, we identified a role for gut microbial metabolites in the regulation of differential IgA production to maintain mucosal homeostasis.

  Jul. 2021, Nature, 595(7868) (7868), 560 - 564, English, International magazine

  [Refereed]

  Scientific journal


• Human gain-of-function STAT1 mutation disturbs IL-17 immunity in mice.

  Moe Tamaura, Naoko Satoh-Takayama, Miyuki Tsumura, Takaharu Sasaki, Satoshi Goda, Tomoko Kageyama, Seiichi Hayakawa, Shunsuke Kimura, Takaki Asano, Manabu Nakayama, Haruhiko Koseki, Osamu Ohara, Satoshi Okada, Hiroshi Ohno, Masao Kobayashi

  Gain-of-function (GOF) mutations in the gene for signal transducer and activator of transcription 1 (STAT1) account for approximately one-half of patients with chronic mucocutaneous candidiasis (CMC) disease. Patients with GOF-STAT1 mutations display a broad variety of infectious and autoimmune manifestations in addition to CMC, and those with severe infections and/or autoimmunity have a poor prognosis. The establishment of safe and effective treatments based on a precise understanding of the molecular mechanisms of this disorder is required to improve patient care. To tackle this problem, we introduced the human R274Q GOF mutation into mice [GOF-Stat1 knock-in (GOF-Stat1R274Q)]. To investigate the immune responses, we focused on the small intestine (SI), which contains abundant Th17 cells. Stat1R274Q/R274Q mice showed excess phosphorylation of STAT1 in CD4+ T cells upon IFN-γ stimulation, consistent with the human phenotype in patients with the R274Q mutation. We identified two subpopulations of CD4+ T cells, those with 'normal' or 'high' level of basal STAT1 protein in Stat1R274Q/R274Q mice. Upon IFN-γ stimulation, the 'normal' level CD4+ T cells were more efficiently phosphorylated than those from WT mice, whereas the 'high' level CD4+ T cells were not, suggesting that the level of STAT1 protein does not directly correlate with the level of pSTAT1 in the SI. Inoculation of Stat1R274Q/R274Q mice with Candida albicans elicited decreased IL-17-producing CD4+RORγt+ cells. Stat1R274Q/R274Q mice also excreted larger amounts of C. albicans DNA in their feces than control mice. Under these conditions, there was up-regulation of T-bet in CD4+ T cells. GOF-Stat1R274Q mice thus should be a valuable model for functional analysis of this disorder.

  Apr. 2020, International immunology, 32(4) (4), 259 - 272, English, International magazine

  [Refereed]

  Scientific journal


• Innate Lymphoid Cells in the Induction of Obesity.

  Takaharu Sasaki, Kazuyo Moro, Tetsuya Kubota, Naoto Kubota, Tamotsu Kato, Hiroshi Ohno, Susumu Nakae, Hirohisa Saito, Shigeo Koyasu

  Complex interactions between immune cells are an important component in the induction of obesity. Here, we show that Il2rg-/-Rag2-/- mice lacking all lymphocytes are resistant to diet-induced obesity. Transplantation of bone marrow cells from Rag2-/- mice, which lack only acquired immune cells, into Il2rg-/-Rag2-/- mice abolishes this resistance, indicating a role for innate lymphoid cells (ILCs) in this process. Mice lacking ILC2 or ILC3 cells, but not natural killer cells, are resistant to obesity. Adoptive transfer of naive ILC2s isolated from the small intestine (SI), but not ILC2s from white adipose tissue (WAT), restores the induction of diet-induced obesity in Il2rg-/-Rag2-/- mice. Analysis of transcriptional differences reveals that SI-ILC2s express higher levels of IL-2 than do WAT-ILC2s and that blockade of IL-2 signaling impairs weight gain and reduces the populations of ILC2s and ILC3s in the SI, suggesting a role for the IL-2/ILC2/3 axis in the induction of obesity.

  Lead, Jul. 2019, Cell reports, 28(1) (1), 202 - 217, English, International magazine

  [Refereed]

  Scientific journal


• Dietary Antigens Induce Germinal Center Responses in Peyer's Patches and Antigen-Specific IgA Production.

  Satoko Hara, Takaharu Sasaki, Naoko Satoh-Takayama, Takashi Kanaya, Tamotsu Kato, Yui Takikawa, Masumi Takahashi, Naoko Tachibana, Kwang Soon Kim, Charles D Surh, Hiroshi Ohno

  The primary induction sites for intestinal IgA are the gut-associated lymphoid tissues (GALT), such as Peyer's patches (PPs) and isolated lymphoid follicles (ILFs). The commensal microbiota is known to contribute to IgA production in the gut; however, the role of dietary antigens in IgA production is poorly understood. To understand the effect of dietary antigens on IgA production, post-weaning mice were maintained on an elemental diet without any large immunogenic molecules. We found that dietary antigens contribute to IgA production in PPs through induction of follicular helper T cells and germinal center B cells. The role of dietary antigens in the PP responses was further confirmed by adding bovine serum albumin (BSA) into the elemental diet. Although dietary antigens are important for PP responses, they have fewer effects than the microbiota on the development and maturation of ILFs. Furthermore, we demonstrated that dietary antigens are essential for a normal antigen-specific IgA response to Salmonella typhi serovar Typhimurium infection. These results provide new insights into the role of dietary antigens in the regulation of mucosal immune responses.

  Lead, 2019, Frontiers in immunology, 10, 2432 - 2432, English, International magazine

  [Refereed]

  Scientific journal


• IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium for antigen uptake.

  Toshi Jinnohara, Takashi Kanaya, Koji Hase, Sayuri Sakakibara, Tamotsu Kato, Naoko Tachibana, Takaharu Sasaki, Yusuke Hashimoto, Toshiro Sato, Hiroshi Watarai, Jun Kunisawa, Naoko Shibata, Ifor R Williams, Hiroshi Kiyono, Hiroshi Ohno

  Interleukin-22 (IL-22) acts protectively and harmfully on intestinal tissue depending on the situation; therefore, IL-22 signaling needs to be tightly regulated. IL-22 binding protein (IL-22BP) binds IL-22 to inhibit IL-22 signaling. It is expressed in intestinal and lymphoid tissues, although its precise distribution and roles have remained unclear. In this study, we show that IL-22BP is highly expressed by CD11b+CD8α- dendritic cells in the subepithelial dome region of Peyer's patches (PPs). We found that IL-22BP blocks IL-22 signaling in the follicle-associated epithelium (FAE) covering PPs, indicating that IL-22BP plays a role in regulating the characteristics of the FAE. As expected, FAE of IL-22BP-deficient (Il22ra2-/-) mice exhibited altered properties such as the enhanced expression of mucus and antimicrobial proteins as well as prominent fucosylation, which are normally suppressed in FAE. Additionally, Il22ra2-/- mice exhibited the decreased uptake of bacterial antigens into PPs without affecting M cell function. Our present study thus demonstrates that IL-22BP promotes bacterial uptake into PPs by influencing FAE gene expression and function.

  Jun. 2017, The Journal of experimental medicine, 214(6) (6), 1607 - 1618, English, International magazine

  [Refereed]

  Scientific journal


• 食餌誘導性肥満における自然リンパ球の機能解析

  佐々木崇晴

  Lead, Mar. 2016, Japanese

  [Refereed]

  Doctoral thesis


• Resolvins as regulators of the immune system.

  Hiroyuki Seki, Takaharu Sasaki, Tomomi Ueda, Makoto Arita

  Inflammation is the first response of the immune system to infection or injury, but excessive or inappropriate inflammatory responses contribute to a range of acute and chronic human diseases. Clinical assessment of dietary supplementation of ù-3 polyunsaturated fatty acids (i.e., eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) indicate that they have beneficial impact on these diseases, although the mechanisms are poorly understood at the molecular level. In this decade, it has been revealed that EPA and DHA are enzymatically converted to bioactive metabolites in the course of acute inflammation and resolution. These metabolites were shown to regulate immune cell functions and to display potent anti-inflammatory actions both in vitro and in vivo. Because of their ability to resolve an acute inflammatory response, they are referred to as proresolving mediators, or resolvins. In this review, we provide an overview of the formation and actions of these lipid mediators.

  May 2010, TheScientificWorldJournal, 10, 818 - 31, English, International magazine

  [Refereed]

  Scientific journal

• Conference report: The 5th Aquaphotomics International Conference

  Takaharu Sasaki, Lawrence K. F. Wong, Roumiana Tsenkova

  Lead, Dec. 2025, JOURNAL OF NEAR INFRARED SPECTROSCOPY, 33(5-6) (5-6), 149 - 154, English

  Others


• The 5th Aquaphotomics International Conference report: Celebrating 20 years

  Takaharu Sasaki, Roumiana Tsenkova

  Lead, Sep. 2025, NIR news


• Regulation of intestinal tumors by food antigens.

  佐々木崇晴, 大野博司

  Lead, 2025, 月刊臨床免疫・アレルギー科, 83(1) (1), Japanese

  Introduction commerce magazine


• FADS1/2二重欠損マウスを用いた新規PUFA欠乏モデルの開発

  安藤美沙, 安藤美沙, 李賢哲, 佐々木崇晴, 横溝岳彦

  2023, 脂質生化学研究, 65, Japanese

  Introduction commerce magazine


• 肥満における腸内細菌と自然リンパ球の相互作用解析

  佐々木 崇晴

  (公財)上原記念生命科学財団, Dec. 2021, 上原記念生命科学財団研究報告集, 35, 1 - 4, Japanese

  Others


• Induction of immunoglobulin A by dietary antigen.

  佐々木崇晴, 大野博司

  Lead, (有)科学評論社, Jan. 2021, 月刊臨床免疫・アレルギー科, 75(1) (1), 109 - 114, Japanese


• 肥満の誘導における自然リンパ球の役割

  佐々木 崇晴, 茂呂 和世, 小安 重夫

  Lead, (有)科学評論社, Feb. 2020, 臨床免疫・アレルギー科, 73(2) (2), 220 - 227, Japanese


• 【代謝調節における免疫細胞の役割】脂肪組織 M2マクロファージの機能を調節する分子 自然リンパ球による肥満の調節

  佐々木 崇晴, 茂呂 和世

  Lead, 医歯薬出版(株), May 2016, 医学のあゆみ, 257(6) (6), 633 - 637, Japanese


• 肥満・インスリン抵抗性におけるナチュラルヘルパー細胞の機能解析

  佐々木 崇晴, 茂呂 和世, 窪田 哲也, 窪田 直人, 小安 重夫

  Lead, (一社)日本肥満学会, Sep. 2013, 肥満研究, 19(Suppl.) (Suppl.), 162 - 162, Japanese


• ドコサヘキサエン酸代謝物の包括的メタボローム解析

  横倉 良行, 磯部 洋輔, 佐々木 崇晴, 岩本 涼, 有田 誠, 新井 洋由

  (公社)日本生化学会, Sep. 2011, 日本生化学会大会プログラム・講演要旨集, 84回, 3P - 0066, Japanese


• ω3系脂肪酸の抗炎症作用に関する包括的メタボローム解析

  佐々木 崇晴, 磯部 洋輔, 中西 広樹, 田口 良, 有田 誠, 新井 洋由

  Lead, (公社)日本薬学会, Mar. 2010, 日本薬学会年会要旨集, 130年会(3) (3), 118 - 118, Japanese

  Summary national conference


• 【脂質代謝のup to date】n-3系脂肪酸の抗炎症作用についての新しい分子生物学的展開

  佐々木 崇晴, 磯部 洋輔, 有田 誠

  Lead, 日本外科代謝栄養学会, Dec. 2009, 外科と代謝・栄養, 43(6) (6), 155 - 160, Japanese


• 脂質の新機能 オメガ3脂肪酸合成酵素FAT-1トランスジェニックマウスの解析(Characterization of Fat-1 transgenic mice rich in endogenous omega-3 polyunsaturated fatty acids)

  有田 誠, 磯部 洋輔, 佐々木 崇晴, 中西 広樹, 田口 良, 新井 洋由

  (公社)日本生化学会, Nov. 2008, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 81回・31回, 3S12 - 3, English

  Summary national conference

• 細胞培養最適化を実現する超ハイスループット培地調液と高精度トランスクリプトーム解析の統合

  佐藤祐哉, 金雅覽, 廣中謙一, 林さくら, 杉野隆一, 蝉克憲, 佐々木崇晴, 新井華子, 福田雅和

  日本再生医療学会総会(Web), 2025, Japanese


• 全遺伝子発現情報を評価指標とした新規ベイズ最適化法による細胞培養条件探索

  田中健太郎, 林さくら, 廣中謙一, 佐藤祐哉, 金雅覽, 蝉克憲, 佐々木崇晴, 新井華子, 福田雅和

  日本再生医療学会総会(Web), 2025, Japanese


• 重篤な脂肪肝を引き起こす高度不飽和脂肪酸欠乏モデルマウスの開発

  安藤美沙, 安藤美沙, 李賢哲, 佐々木崇晴, 横溝岳彦

  日本生化学会大会(Web), 2023, Japanese


• 高脂肪食による肥満の誘導における自然リンパ球の役割

  佐々木崇晴

  東京免疫フォーラム, Mar. 2021, Japanese

  [Invited]

  Invited oral presentation


• Involvement of innate lymphoid cells in the induction of diet-induced obesity.

  Takaharu Sasaki, Kazuyo Moro, Tetsuya Kubota, Naoto Kubota, Hiroshi Ohno, Shigeo Koyasu

  ILC 2018 The 3rd International Conference on Innate Lymphoid Cells, Nov. 2018

  Poster presentation


• Role of innate lymphoid cells in the induction of obesity

  Takaharu Sasaki, Kazuyo Moro, Tetsuya Kubota, Naoto Kubota, Tamotsu Kato, Hiroshi Ohno, Shigeo Koyasu

  GI research achademy, May 2018

  Public symposium


• Involvement of group 2 ILCs in the induction of obesity.

  Takaharu Sasaki, Kazuyo Moro, Tetsuya Kubota, Naoto Kubota, Tamotsu Kato, Hiroshi Ohno, Shigeo Koyasu

  18th International Congress of Mucosal Immunology, Jul. 2017

  Oral presentation


• Involvement of innate lymphoid cells in the induction of obesity.

  Takaharu Sasaki, Kazuyo Moro, Shigeo

  University of Strasbourg-RIKEN Workshop on Membrane Lipidology, Mar. 2017

  Nominated symposium


• Involvement of innate lymphoid cells in the induction of obesity

  Takaharu Sasaki, Kazuyo Moro, Tetsuya Kubota, Naoto Kubota, Tadashi Kadowaki and Shigeo Koyasu

  Environment controlling normal and diseased hematopoietic and immune systems, Mar. 2016

  Poster presentation


• Involvement of Natural Helper cells, a member of group 2 ILCs (ILC2) in the induction of obesity.

  Takaharu Sasaki, Kazuyo Moro and Shigeo Koyasu

  第44回 日本免疫学会学術集会, Nov. 2015

  Oral presentation


• Role of Natural Helper cells, a member of group 2 ILC (ILC2s), in obesity

  Takaharu Sasaki, Kazuyo Moro, Shigeo Koyasu

  第43回 日本免疫学会学術集会, Dec. 2014

  Oral presentation


• Role of innate lymphoid cells (ILCs) in the induction of diet-induced obesity.

  Takaharu Sasaki, Kazuyo Moro, Tetsuya Kubota, Naoto Kubota, Tadashi Kadowaki, Shigeo Koyasu

  2014 CSI Congress on Immunology, Oct. 2014

  Invited oral presentation


• Involvement of Natural Helper cells in the onset of diet-induced obesity.

  Takaharu Sasaki, Kazuyo Moro, Tetsuya Kubota, Naoto Kubota, Shigeo Koyasu

  22nd International Symposium on Molecular and Cell Biology of Macrophages: MMCB2014, Jun. 2014

  Poster presentation


• Role of Natural Helper cells in obesity

  Takaharu Sasaki, Kazuyo Moro, Shigeo Koyasu

  第42回 日本免疫学会学術集会, Dec. 2013

  Oral presentation


• 肥満の誘導における ナチュラルヘルパー細胞の機能解析

  佐々木崇晴, 茂呂和世, 窪田哲也, 窪田直人, 小安重夫

  日本肥満学会（第34回）, Oct. 2013

  Oral presentation


• The role of Natural Helper cells in obesity-associated insulin resistance

  Takaharu Sasaki, Kazuyo Moro, Tetsuya Kubota, Naoto Kubota, Shigeo Koyasu

  6th International Workshop of Kyoto T Cell Conference (KTCC2013), Jun. 2013

  Poster presentation


• The role of Natural Helper cells in obesity-associated insulin resistance

  21st International Symposium on Molecular and Cell Biology of Macrophages: MMCB2013, May 2013

  Poster presentation


• ω3系脂肪酸の抗炎症作用に関する包括的メタボローム解析

  佐々木崇晴, 磯部洋輔, 中西広樹, 田口良, 有田誠, 新井洋由

  日本薬学会 第130年会, Mar. 2010

  Poster presentation


• ω3系脂肪酸の抗炎症作用に関する包括的メタボローム解析

  佐々木崇晴, 磯部洋輔, 中西広樹, 田口良, 有田誠, 新井洋由

  第8回 次世代を担う若手ファーマ・バイオフォーラム 2009, Dec. 2009

  Oral presentation

• 日本肥満学会

  2013 - Present


• 日本免疫学会

  2012 - Present

• 腸管免疫系における高度不飽和脂肪酸の機能解析

  佐々木 崇晴

  日本学術振興会, 科学研究費助成事業 基盤研究(C), 順天堂大学, Apr. 2023 - Mar. 2026


• 肥満を誘導する自然リンパ球を介した腸内細菌機能制御機構の解析

  佐々木 崇晴

  公益財団法人 武田科学振興財団, 医学系研究助成（基礎）, 国立研究開発法人理化学研究所, Aug. 2021 - Mar. 2024, Principal investigator


• 食物抗原が消化器腫瘍を抑制する機構の解析

  佐々木 崇晴

  日本学術振興会, 科学研究費助成事業 若手研究, 国立研究開発法人理化学研究所, Apr. 2021 - Mar. 2023

  AOM/DSS投与によって消化器腫瘍を誘導したマウスに無抗原食を摂食させると、1回目の実験では腫瘍部位においてLgr5などのがん幹細胞マーカーの発現が顕著に増加することを見出していたことから食物抗原が癌幹細胞の増加させることが示唆された。その再現性を確認したところ、2回目の実験では1回目の実験のような顕著なLgr5の発現増加は見られなかった。したがって、1回目の実験において見られたLgr5発現の増加は食物抗原そのものではなく、無抗原食によってもたらされる腸内細菌叢の変化によってもたらされたものであることが示唆された。1回目の実験における糞便を用いて腸内細菌の解析を行ったところ、無抗原食群ではLgr5の発現と正の相関を示す細菌が3種、負の相関を示す細菌が2種類見つかった。さらに、糞便中の水溶性代謝物の解析をLC-MSによって行ったところ、腫瘍の悪化に関与することが知られる代謝物がLgr5の発現と正の相関を示した。即ち、1回目の実験では無抗原食の摂食によって増加した細菌によって産生される代謝物がLgr5の増加を促した可能性が考えられた。2回目の実験では異なる腸内細菌の組成となったことでLgr5の発現上昇が見られなかったと考えられる。以上の結果は腸内細菌と腫瘍との関係性を探る研究上で重要ではあるが、食物抗原が消化器腫瘍に及ぼす影響について探る本研究課題の趣旨とは異なる為、腸内細菌についての解析はここで保留とした。 一方、これまでに消化器腫瘍を自然発症するAPCminマウスにおいて食物抗原がその腫瘍形成を抑制する研究結果を得ていたので、次年度はそのメカニズムについて調べていく研究に方向転換することとした。


• Can food antigen be a factor regulating intestinal tumorigenesis?

  Sasaki Takaharu

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, Institute of Physical and Chemical Research, Apr. 2019 - Mar. 2022

  Gut is constantly exposed to various components such as food ingredients and microbiota. It has been reported that food antigen can induce small intestinal immune system. In this study, we aimed to examine whether food antigen acts as a regulator of intestinal tumorigenesis. By utilizing APCmin mice, which spontaneously give rise to intestinal tumorigenesis, we discovered that food antigen suppresses small intestinal tumorigenesis. Besides, Peyer's patches had a role in the suppression of the tumorigenesis, and were involved in the induction of small intestinal immune cells by food antigen. These data suggest that induction of intestinal immune cells by food antigen via Peyer's patches suppresses small intestinal tumorigenesis.


• 肥満における腸内細菌と自然リンパ球の相互作用解析

  佐々木 崇晴

  公益財団法人 上原記念生命科学財団, 研究奨励金, 国立研究開発法人理化学研究所, Jan. 2020 - Apr. 2021, Principal investigator


• Role of innate lymphoid cells in adipose tissue homeostasis

  Koyasu Shigeo, Sasaki Takaharu, Ealey Kafi N.

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A), Grant-in-Aid for Scientific Research (A), Institute of Physical and Chemical Research, Apr. 2016 - Mar. 2019

  Using Rag2-/- mice lacking adaptive immune cells and γc-/-Rag2-/- mice lacking all lymphocytes, we have revealed that group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) from small intestine (SI-ILC2 and SI-ILC3, respectively) and IL-2 derived from those SI-ILCs are involved in the diet-induced obesity. Contrary to SI-ILC2, ILC2 derived from white adipose tissue (WAT-ILC2) suppressed adipocyte differentiation in an in vitro culture system, indicating that SI-ILC2 and WAT-ILC2 have different functions.