Kimura, Shunsuke

写真a

Affiliation

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

Position

Associate Professor

 

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

  • Macrophage ubiquitin-specific protease 2 contributes to motility, hyperactivation, capacitation, and in vitro fertilization activity of mouse sperm

    M Hashimoto, S Kimura, C Kanno, Y Yanagawa, T Watanabe, J Okabe, ...

    Cellular and Molecular Life Sciences, 1-20  2020.10

    Research paper (scientific journal), Joint Work, Except for reviews,  ISSN  1420-682X

     View Summary

    Macrophages are innate immune cells that contribute to classical immune functions and tissue homeostasis. Ubiquitin-specific protease 2 (USP2) controls cytokine production in macrophages, but its organ-specific roles are still unknown. In this study, we generated myeloid-selective Usp2 knockout (msUsp2KO) mice and specifically explored the roles of testicular macrophage-derived USP2 in reproduction. The msUsp2KO mice exhibited normal macrophage characteristics in various tissues. In the testis, macrophage Usp2 deficiency negligibly affected testicular macrophage subpopulations, spermatogenesis, and testicular organogenesis. However, frozen-thawed sperm derived from msUsp2KO mice exhibited reduced motility, capacitation, and hyperactivation. In addition, macrophage Usp2 ablation led to a decrease in the sperm population exhibiting high intracellular pH, calcium influx, and mitochondrial membrane potential. Interrupted pronuclei formation in eggs was observed when using frozen-thawed sperm from msUsp2KO mice for in vitro fertilization. Administration of granulocyte macrophage-colony stimulating factor (GM-CSF), whose expression was decreased in testicular macrophages derived from msUsp2KO mice, restored mitochondrial membrane potential and total sperm motility. Our observations demonstrate a distinct role of the deubiquitinating enzyme in organ-specific macrophages that directly affect sperm function.

  • Osteoprotegerin-dependent M-cell self-regulation balances gut infection and immunity.

    Kimura S, Nakamura Y, Kobayashi N, Shiroguchi K, Kawakami E, Mutoh M, Takahashi-Iwanaga H, Yamada T, Hisamoto M, Nakamura M, Udagawa N, Sato S, Kaisho T, Iwanaga T, and Hase K

    Nature communications 11 ( 1 ) 234 - 234 2020.01

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    Microfold cells (M cells) are responsible for antigen uptake to initiate immune responses in the gut-associated lymphoid tissue (GALT). Receptor activator of nuclear factor-κB ligand (RANKL) is essential for M cell differentiation. Follicle-associated epithelium (FAE) covers the GALT and is continuously exposed to RANKL from stromal cells underneath the FAE, yet only a subset of FAE cells undergoes differentiation into M cells. Here, we show that M cells express osteoprotegerin (OPG), a soluble inhibitor of RANKL, which suppresses the differentiation of adjacent FAE cells into M cells. Notably, OPG deficiency increases M cell number in the GALT and enhances commensal bacterium-specific immunoglobulin production, resulting in the amelioration of disease symptoms in mice with experimental colitis. By contrast, OPG-deficient mice are highly susceptible to Salmonella infection. Thus, OPG-dependent self-regulation of M cell differentiation is essential for the balance between the infectious risk and the ability to perform immunosurveillance at the mucosal surface.

  • The Roles of Peyer's Patches and Microfold Cells in the Gut Immune System: Relevance to Autoimmune Diseases.

    Kobayashi N, Takahashi D, Takano S, Kimura S and Hase K.

    Front. Immunol 10   2345 2019.10

    Research paper (scientific journal), Joint Work, Accepted

  • Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis.

    Nishida K, Hasegawa A, Yamasaki S, Uchida R, Ohashi W, Kurashima Y, Kunisawa J, Kimura S, Iwanaga T, Watarai H, Hase K, Ogura H, Nakayama M, Kashiwakura JI, Okayama Y, Kubo M, Ohara O, Kiyono H, Koseki H, Murakami M, Hirano T

    Scientific reports 9 ( 1 ) 10842 - 10842 2019.07

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency and skin disorders. Various cells including mast cells release Zn-containing granules when activated; however, the biological role of the released Zn is currently unclear. Here we report our findings that Zn transporter ZnT2 is required for the release of Zn from mast cells. In addition, we found that Zn and mast cells induce IL-6 production from inflammatory cells such as skin fibroblasts and promote wound healing, a process that involves inflammation. Zn induces the production of a variety of pro-inflammatory cytokines including IL-6 through signaling pathways mediated by the Zn receptor GPR39. Consistent with these findings, wound healing was impaired in mice lacking IL-6 or GPR39. Thus, our results show that Zn and mast cells play a critical role in wound healing through activation of the GPR39/IL-6 signaling axis.

  • Airway M cells arise in the lower airway due to RANKL signaling and reside in the bronchiolar epithelium associated with iBALT in murine models of respiratory disease

    Shunsuke Kimura*, Mami Mutoh, Meri Hisamoto, Hikaru Saito, Shun Takahashi, Takanori Asakura, Makoto Ishii, Yutaka Nakamura, Junichiro Iida, Koji Hase and Toshihiko Iwanaga

    Frontiers in Immunology 10   1323 2019.06

    Research paper (scientific journal), Joint Work, Accepted

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

Reviews, Commentaries, etc. 【 Display / hide

  • 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

    Introduction and explanation (commerce magazine), Joint Work

  • マクロファージ選択的ユビキチン特異的プロテアーゼ2欠損マウスの精巣機能の評価

    天笠美聡, 菅野智裕, 木村俊介, 柳川洋二郎, 岩永敏彦, 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 161st   478 2018.08

    Other article, Joint Work,  ISSN  1347-8621

  • マクロファージの新たな機能制御分子による2型糖尿病関連分子の発現調節

    北村浩, 伊藤誠敏, 木村俊介, 嶋本良則, 小林敦夫, 菊口千智, 岡部潤, 渡会浩志, 小原收, 三好一郎

    日本獣医学会学術集会講演要旨集 ((公社)日本獣医学会)  152nd   322 - 322 2011.08

    Other article, Joint Work,  ISSN  1347-8621

  • Essential role of membrane trafficking factor AP-1B in gut immune homeostasis

    Daisuke Takahashi, Koji Hase, Shunsuke Kimura, Hiroshi Ohno

    JOURNAL OF IMMUNOLOGY (AMER ASSOC IMMUNOLOGISTS)  184 2010.04

    Summary of the papers read (international conference), Joint Work,  ISSN  0022-1767

  • Molecular Mechanisms and Biological Significance of Autophagosome Movement

    木村俊介, 吉森保

    細胞工学 25 ( 11 ) 1273 - 1279 2006.10

    Other article, Joint Work,  ISSN  0287-3796

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Presentations 【 Display / hide

  • 腸管ならびに呼吸器粘膜における RANKL-RANK-OPG による M 細胞の分化制御機構

    木村俊介

    第61回歯科基礎医学会学術大会, 2019.10, Symposium, Workshop, Panelist (nomination)

  • M細胞による抗原の取り込みと粘膜免疫系の制御

    木村俊介

    第18回お茶の水眼アレルギー研究会, 2019.06, Other

  • 粘膜免疫の最前線で働くM細胞の歴史と最近の知見

    木村俊介

    平成29年度日本解剖学会リンパ・免疫系懇話会, 2018.03, Other

  • Molecular mechanisms of plasma membrane deformation by M-Sec during TNT formation

    Shunsuke Kimura

    GSK meeting Tunneling Nanotubes (TNTs) – Cell-to-Cell Social Networking in Disease Conference, 2016.09, Other

  • RANKL-RANKシグナルによる腸特殊上皮M細胞分化制御機構の解明

    木村俊介

    松本歯科大学大学院歯学独立研究科大学院セミナー, 2015.11, Other

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

  • 呼吸器M細胞の分化機構と疾患における機能の解明

    2019.04
    -
    2022.03

    Hokkaido University, 木村 俊介, 久本 芽璃, Grant-in-Aid for Scientific Research (C)

     View Summary

    呼吸は生命維持に必要な活動です。呼吸器は鼻からはじまり気管を通して肺へとつながります。空気の通り道である気道には空気中の病原菌、アレルギーの原因となるアレルゲンが大量に存在し、呼吸とともに体内へと入ってきます。そのため、呼吸器では免疫系が発達しています。M細胞は腸管で研究がすすむ、粘膜免疫応答に重要な細胞です。一方で、呼吸器におけるM細胞については不明な点が多く残されています。本研究計画では呼吸器M細胞の性状、機能、呼吸器疾患との関係を明らかにすることを目的としています。

  • Molecular mechanisms underlying differentiation of intestinal M cells

    2016.04
    -
    2019.03

    Hokkaido University, Kimura Shunsuke, KOBAYASHI nobuhide, Grant-in-Aid for Scientific Research (C)

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    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.

  • Host-microbe interaction mediated by intestinal M cells

    2013.04
    -
    2016.03

    The University of Tokyo, Hase Koji, MIMURO Hitomi, FURUSAWA Yukihiro, KIMURA Shunsuke, Grant-in-Aid for Scientific Research (B)

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    It remains unknown whether M-dependent antigen uptake also contributes to cellular immunity against mucosal pathogens. Here we investigated the contribution of M cells to Th17-dependent cellular immunity. Wild type (WT) and M-cell-null mice were orally infected with Citrobacter rodentium. After the infection, M-cell-null mice developed more severe infectious colitis compared to WT mice, as evidenced by exacerbation of body weight loss and fecal clinical scores. Importantly, colonic Th17 cells were decreased in M-cell-null mice compared to WT mice at the early phase of infection. In contrast, under the physiological conditions, there was no significant difference in the number of colonic Th17 cells between the two groups. Collectively, these results suggested that M-cell-dependent antigen uptake plays a key role in the protection against C. rodentium infection by facilitating antigen-specific Th17 induction.

  • Modulatory effects of macrophage M-mod/USP2 on type2 diabetes

    2012.04
    -
    2015.03

    Nagoya City University, KITAMURA Hiroshi, MIYOSHI Ichiro, OKAMOTO Shiki, NAOE Yoshinori, TAKAHASI Eiki, IWANAGA Toshihiko, KIMURA Shunsuke, Grant-in-Aid for Scientific Research (C)

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    1) In ob/ob mice, M-mod/USP2A expression was clearly decreased in adipose tissue macrophages whereas aP2 and PAI were increased. Transgenic mice selectively expressing M-mod in macrophages did not exhibited significant changes in body weight gain, blood glucose levels, and blood insulin levels after high fat diet for 3 months. On the other hand, the M-mod transgenic mice displayed decreased accumulation of macrophages in visceral adipose tissues in parallel with decreased expression of chemokines in macrophages. In addition, M-mod overexpression in macrophages for 1 year caused decreased body weight gain and improved insulin sensitivity. Thus, M-mod seems to be a potent attenuator of type 2 diabetes.
    2) M-mod knockdown macrophage-like cells modulated acetylation and methylation of histone near the M-mod-targeting genes such as aP2. Moreover, we found several nuclear proteins directly associated with M-mod in macrophages.

  • The possibility of M-cell differentiation regulated by novel intercellular communication system

    2012.04
    -
    2015.03

    Hokkaido University, YAMAKAMI-KIMURA Megumi, KIMURA Shunsuke, Grant-in-Aid for Young Scientists (B)

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    M-Sec is a cytoplasmic protein expressed by macrophages and intestinal microfold cells (M cells). We have previously reported that M-Sec in macrophage induces plasma membrane deformation resulting in membrane nanotube; however function of M-Sec in M cells as well as the existence of membrane nanotubes has been largely unknown. M cells are specialized epithelial cells reside in follicle-associated epithelium of Peyer’s patches, and have uptake capacity of luminal macromolecules. Differentiation of M cells is thought to be regulated by the interaction with stromal cells underneath epithelial basement membrane. In the present study, we found that M cell had membrane protrusions on the basolateral membrane. The protrusions were elongated across basement membrane and reached to stromal cells. On the other hand, M-Sec KO mice did not show clear phenotype in the protrusion formation and M-cell differentiation, suggesting the probability that other molecules compensate the function of M-Sec.

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Courses Taught 【 Display / hide

  • STUDY OF MAJOR FIELD: (BIOCHEMISTRY)

    2021

  • SEMINAR: (BIOCHEMISTRY)

    2021

  • RESEARCH FOR BACHELOR'S THESIS 1

    2021

  • PHARMACEUTICAL-ENGLISH SEMINAR

    2021

  • IMMUNOLOGY AND METABOLISM

    2021

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