Kimura, Shunsuke



Faculty of Pharmacy, Department of Pharmaceutical Sciences 生化学講座 (Shiba-Kyoritsu)


Associate Professor

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Career 【 Display / hide

  • 2019.10

    Japan Science and Technology Agency


Research Keywords 【 Display / hide

  • パイエル板


Books 【 Display / hide

  • マウス組織アトラス

    岩永 敏彦, 小林 純子, 木村 俊介( 医学), 医学書院, 2019

  • 新編カラーアトラス組織・細胞学

    岩永 敏彦, 木村 俊介( 医学), 小林 純子, 医歯薬出版, 2017

Papers 【 Display / hide

  • Purified diet affects intestinal epithelial proliferation and barrier functions through gut microbial alterations.

    Hiroaki Shiratori, Kisara M Hattori, Kazuaki Nakata, Takuma Okawa, Seiga Komiyama, Yusuke Kinashi, Yuma Kabumoto, Yuria Kaneko, Motoyoshi Nagai, Tomoko Shindo, Nobuko Moritoki, Yuki I Kawamura, Taeko Dohi, Daisuke Takahashi, Shunsuke Kimura, Koji Hase

    International immunology  2024.01

    Research paper (scientific journal), Accepted

     View Summary

    The gut microbiota plays a crucial role in maintaining epithelial barrier function. Although multiple studies have demonstrated the significance of dietary factors on gut microbiota and mucosal barrier function, the impact of a purified diet, which has long been used in various animal experiments, on intestinal homeostasis remains to be elucidated. Here, we compared the impact of two different types of diets, a crude diet and an AIN-93G-formula purified diet, on epithelial integrity and the gut microbiota. Purified diet-fed mice exhibited shorter villi and crypt lengths and slower epithelial turnover, particularly in the ileum. In addition, antimicrobial products, including islet-derived protein 3γ (REG3γ), were substantially decreased in purified diet-fed mice. Purified diet feeding also suppressed α1,2-fucosylation on the epithelial surface. Furthermore, purified diet induced metabolic rewiring to fatty acid oxidation and ketogenesis. 16S ribosomal RNA gene sequencing of the ileal contents and mucus layer revealed distinct gut microbiota compositions between the purified and crude diet-fed mice. Purified diet feeding reduced the abundance of segmented filamentous bacteria (SFB), which potently upregulate REG3γ and fucosyltransferase 2 (Fut2) by stimulating group 3 innate lymphoid cells (ILC3) to produce IL-22. These observations illustrate that the intake of a crude diet secures epithelial barrier function by facilitating SFB colonization, whereas a purified diet insufficiently establishes the epithelial barrier, at least partly owing to the loss of SFB. Our data suggest that the influence of purified diets on the epithelial barrier integrity should be considered in experiments using purified diets.

  • Dysfunction of Foxp3+ Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal Lumen.

    Kouhei Koshida, Mitsuki Ito, Kyosuke Yakabe, Yoshimitsu Takahashi, Yuki Tai, Ryouhei Akasako, Tatsuki Kimizuka, Shunsuke Takano, Natsumi Sakamoto, Kei Haniuda, Shuhei Ogawa, Shunsuke Kimura, Yun-Gi Kim, Koji Hase, Yohsuke Harada

    International journal of molecular sciences 24 ( 10 )  2023.05

    Research paper (scientific journal), Accepted

     View Summary

    Foxp3+ regulatory T (Treg) cells prevent excessive immune responses against dietary antigens and commensal bacteria in the intestine. Moreover, Treg cells contribute to the establishment of a symbiotic relationship between the host and gut microbes, partly through immunoglobulin A. However, the mechanism by which Treg cell dysfunction disturbs the balanced intestinal microbiota remains unclear. In this study, we used Foxp3 conditional knockout mice to conditionally ablate the Foxp3 gene in adult mice and examine the relationship between Treg cells and intestinal bacterial communities. Deletion of Foxp3 reduced the relative abundance of Clostridia, suggesting that Treg cells have a role in maintaining Treg-inducing microbes. Additionally, the knockout increased the levels of fecal immunoglobulins and immunoglobulin-coated bacteria. This increase was due to immunoglobulin leakage into the gut lumen as a result of loss of mucosal integrity, which is dependent on the gut microbiota. Our findings suggest that Treg cell dysfunction leads to gut dysbiosis via aberrant antibody binding to the intestinal microbes.

  • Protective effect of the tunneling nanotube-TNFAIP2/M-sec system on podocyte autophagy in diabetic nephropathy.

    Barutta F, Bellini S, Kimura S, Hase K, Corbetta B, Corbelli A, Fiordaliso F, Bruno S, Biancone L, Barreca A, Papotti MG, Hirsh E, Martini M, Gambino R, Durazzo M, Ohno H, Gruden G

    Autophagy 19 ( 2 ) 505 - 524 2023.02

    Research paper (scientific journal), Accepted,  ISSN  1554-8627

  • GP2-expressing cells: a new guardian with divergent functions in the intestine, eyes, and nose.

    Toshihiko Iwanaga, Shunsuke Kimura

    Biomedical research (Tokyo, Japan) 44 ( 6 ) 233 - 243 2023


     View Summary

    GP (glycoprotein)-2, originally identified as a predominant membranous component of pancreatic acinar cells, has attracted the interest of researchers in mucosal immunology for its role as a functional molecule specific for antigen-sampling cells in the intestinal Peyer's patches. GP2 is involved in the detection of pathological bacteria and is also histologically useful for the identification of the M cell lineage and their differentiation in lymphoid tissues. Subsequent immunohistochemistry for GP2 has revealed a broad distribution of M cells and related cells in the nasopharyngeal lymphoid tissues, conjunctiva, tear duct, and airway. Especially, GP2 cells in the paranasal sinuses and tear duct have been identified as novel types of epithelial cells. The systematic administration of RANKL can induce extra-M cells in conventional epithelia of body. The production and release of GP2 by conjunctival goblet cells and several mucous glands suggests leading roles for mucous cells in protection, including the entrapment of microorganisms for infections. The ocular surface and conjunctiva are connected to the lacrimal sac, nasolacrimal duct, and further nasal cavity, comprising another canal that passes through the body. The broad distribution of GP2-expressingcells may indicate its function as a new guardian in the intestine, eyes, and nose, all of which are exposed to external milieu.

  • Spi-B alleviates food allergy by securing mucosal barrier and immune tolerance in the intestine

    Narumi Ishihara, Yutaka Nakamura, Kyosuke Yakabe, Seiga Komiyama, Yumiko Fujimura, Tsuneyasu Kaisho, Shunsuke Kimura, Koji Hase

    Frontiers in Allergy (Frontiers Media SA)  3   996657 2022.10

    Corresponding author, Accepted,  ISSN  2673-6101

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    Food allergy is a type I allergic reaction induced by mast cells and is mainly activated by allergen-specific immunoglobulin (Ig)E. Spi-B is an E26-transformation-specific (Ets) family transcription factor essential for the differentiation and functional maturation of several immune cell subsets, including mast cells. However, the possible involvement of Spi-B in food allergy remains unclear. In this study, we found that Spi-B-deficient mice were highly susceptible to food allergy to ovalbumin (OVA), as indicated by the exacerbation of diarrhea and elevation of serum IgE levels. These pathological changes were associated with enhanced mast cell infiltration into the intestinal lamina propria. Activation of mast cells in the intestinal mucosa was observed in Spib<sup>−/−</sup> mice, even under physiological conditions. Accordingly, Spi-B deficiency increased the translocation of fluorescently labeled dextran from the lumen to the serum, suggesting increased intestinal permeability in Spib<sup>−/−</sup> mice. Moreover, Spib<sup>−/−</sup> mice showed defects in oral tolerance induction to OVA. These data illustrate that Spi-B suppresses the development of food allergies by controlling the activation of intestinal mast cells and by inducing immune tolerance to food allergens.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • OsteoprotegerinによるM細胞数の自己調節は粘膜免疫応答と上皮バリア機構のバランスを制御する

    木村 俊介, 長谷 耕二

    臨床免疫・アレルギー科 ((有)科学評論社)  75 ( 2 ) 194 - 200 2021.02

    Other, Joint Work,  ISSN  1881-1930

  • 【自己免疫疾患と腸内細菌叢】自己免疫疾患における粘膜免疫系の関与 M細胞の潜在的役割

    大谷 祐貴, 木村 俊介, 長谷 耕二

    臨床免疫・アレルギー科 ((有)科学評論社)  75 ( 1 ) 1 - 8 2021.01

    Other, Joint Work,  ISSN  1881-1930

  • マクロファージのユビキチン特異的プロテアーゼ2が凍結精子の機能に与える役割

    橋本茉由子, 木村俊介, 菅野智裕, 柳川洋二郎, 渡邉敬文, 高橋英機, 永野昌志, 北村浩

    日本獣医学会学術集会講演要旨集 164th (CD-ROM) 2021

    ISSN  1347-8621

  • Sox8 is essential for the production of antigen-specific S-IgA during the weaning period by regulating M-cell maturation

    木村 俊介, 長谷 耕二

    Clinical immunology & allergology 73 ( 1 ) 89 - 95 2020.01

    Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Joint Work

  • 精巣マクロファージのユビキチン特異的プロテアーゼ2が精子機能に与える影響

    橋本茉由子, 木村俊介, 菅野智裕, 菅野智裕, 柳川洋二郎, 渡邉敬文, 岡部潤, 高橋英機, 永野昌志, 北村浩

    日本分子生物学会年会プログラム・要旨集(Web) 43rd 2020

    Other, Joint Work

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Presentations 【 Display / hide

  • 下気道におけるM細胞の分化機構の解明

    木村 俊介, 河合 真悟, 山田 恭央, 澤 新一郎, 長谷耕二



    Poster presentation

  • Characterization of M cells in the lower respiratory tract in physiological and pathological conditions

    Shunsuke Kimura, Shingo Kawai, Takahiro Yamada, Yutaka Nakamura, Shinichiro Sawa, Koji Hase



    Oral presentation (general)

  • 呼吸器M細胞による外因性微粒子取り込み機構とその生物学的意義の解明

    木村 俊介、河合 真悟、山田 恭央、中村 有孝、遠藤 真弓、藤村 由美子、澤 新一郎、長谷耕二



    Symposium, workshop panel (public)

  • 下気道におけるM細胞の分化機構の解明

    木村 俊介, 河合 真悟, 長谷耕二



    Oral presentation (general)

  • Regulation mechanisms of mucosal immunity and infection by M cells

    Shunsuke Kimura, Yutaka Nakamura, Nobuhide Kobayashi, Koji Hase



    Symposium, workshop panel (public)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • インフルエンザ感染におけるM細胞の誘導機構と感染病態における役割の解明


    基盤研究(B), Principal investigator

  • 呼吸器M細胞による外因性微粒子取り込み機構とその生物学的意義の解明


    Japan Science and Technology Agency, Strategic Basic Research Programs, さきがけ(微粒子), Research grant, Principal investigator

  • 呼吸器M細胞の分化機構と疾患における機能の解明


    Hokkaido University, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

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  • Molecular mechanisms underlying differentiation of intestinal M cells


    Hokkaido University, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Kimura Shunsuke, KOBAYASHI nobuhide, Grant-in-Aid for Scientific Research (C), No Setting

     View Summary

    Microfold (M) cells residing in the follicle-associated epithelium (FAE) of the gut-associated lymphoid tissue are specialized for antigen uptake to initiate mucosal immune responses. The molecular machinery and biological significance of M cell differentiation, however, remain to be fully elucidated. Here, we demonstrate that Sox8, a member of the SRY-related HMG box transcription factor family, is specifically expressed by M cells in the intestinal epithelium. Sox8 directly binds the promoter region of Gp2 to increase Gp2 expression, which is the hallmark of functionally mature M cells. Furthermore, genetic deletion of Sox8 causes a marked decrease in the number of mature M cells, resulting in reduced antigen uptake in Peyer's patches. Consequently, juvenile Sox8-deficient mice showed attenuated germinal center reactions and antigen-specific IgA responses. These findings indicate that Sox8 plays an essential role in the development of M cells to establish mucosal immune responses.

  • Roles of a novel key regulatory molecule, USP2, in energy homeostasis


    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Hiroshi Kitamura, KIMURA shunsuke, OKAMOTO shiki, TAKAHASHI eiki, OKABE jun, Grant-in-Aid for Scientific Research (C), No Setting

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    By taking advantage of a macrophage-selective transgenic mouse model, we evinced that macrophage ubiquitin-specific protease (USP)2 suppressed adipose tissue inflammation resulting in attenuation of insulin resistance. USP2 inhibited inflammatory cytokine production through modulation of expression ratio of transcription factors OCT1 and OCT2. We also demonstrated that USP2 in hypothalamic nuclei is expressionally regulated by blood glucose level. Moreover, USP2 maintains mitochondrial integrity to efficiently supply ATP in myoblasts. Collectively, USP2 is a key regulatory molecule for energy homeostasis in various cells.

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Awards 【 Display / hide

  • 慶應義塾大学薬学部 学部長賞 研究部門

    2020, 慶應義塾大学薬学部

    Type of Award: Keio commendation etc.

  • 北海道大学大学院医学研究院・大学院医学院・医学部医学科「優秀論文賞」

    2019, 北海道大学

    Type of Award: Other

  • 日本顕微鏡学会第73回学術講演会 優秀ポスター賞(生物部門)

    2017.06, 日本顕微鏡学会, パイエル板M細胞の成熟過程の可視化

    Type of Award: Award from Japanese society, conference, symposium, etc.

  • 日本骨免疫学会ウィンターセミナー優秀演題

    2017.01, 日本骨免疫学会, RANKL-RANKシグナルによる腸上皮特殊細胞M細胞の分化制御

    Type of Award: Award from Japanese society, conference, symposium, etc.

  • 日本解剖学会奨励賞

    2016, 日本解剖学会, 粘膜免疫組織を構成する特殊上皮M細胞の分化機構ならびに発現分子解析

    Type of Award: Award from Japanese society, conference, symposium, etc.

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Courses Taught 【 Display / hide











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