Kimura, Shunsuke

写真a

Affiliation

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

Position

Associate Professor

Related Websites

External Links

 

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

  • Intestinal immunity: to be, or not to be, induced? That is the question.

    Daisuke Takahashi, Shunsuke Kimura, Koji Hase

    International immunology 33 ( 12 ) 755 - 759 2021.08

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0953-8178

     View Summary

    The intestinal immune system maintains intestinal homeostasis in collaboration with diverse immune cell subsets residing at the epithelial layer, lamina propria and gut-associated lymphoid tissue (GALT). Bacterial components and their metabolites are essential for the establishment of the gut immune system. In addition, nutritional signals contribute to maintaining the mucosal immune response. Specialized epithelial microfold (M) cells in GALT facilitate immune surveillance on the mucosal surface by actively taking up external antigens to transport them into the lymphoid follicles. Because hyperplasia of M cells causes an excessive immune response in GALT, there is a self-regulatory mechanism to control the development of M cells appropriately. In this review, we will discuss the molecular mechanisms of mucosal immune regulation and their biological importance.

  • Symbiotic polyamine metabolism regulates epithelial proliferation and macrophage differentiation in the colon.

    Atsuo Nakamura, Shin Kurihara, Daisuke Takahashi, Wakana Ohashi, Yutaka Nakamura, Shunsuke Kimura, Masayoshi Onuki, Aiko Kume, Yukiko Sasazawa, Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, Shinji Saiki, Mitsuharu Matsumoto, Koji Hase

    Nature communications 12 ( 1 ) 2105 - 2105 2021.04

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    Intestinal microbiota-derived metabolites have biological importance for the host. Polyamines, such as putrescine and spermidine, are produced by the intestinal microbiota and regulate multiple biological processes. Increased colonic luminal polyamines promote longevity in mice. However, no direct evidence has shown that microbial polyamines are incorporated into host cells to regulate cellular responses. Here, we show that microbial polyamines reinforce colonic epithelial proliferation and regulate macrophage differentiation. Colonisation by wild-type, but not polyamine biosynthesis-deficient, Escherichia coli in germ-free mice raises intracellular polyamine levels in colonocytes, accelerating epithelial renewal. Commensal bacterium-derived putrescine increases the abundance of anti-inflammatory macrophages in the colon. The bacterial polyamines ameliorate symptoms of dextran sulfate sodium-induced colitis in mice. These effects mainly result from enhanced hypusination of eukaryotic initiation translation factor. We conclude that bacterial putrescine functions as a substrate for symbiotic metabolism and is further absorbed and metabolised by the host, thus helping maintain mucosal homoeostasis in the intestine.

  • Protective Role of the M-Sec-Tunneling Nanotube System in Podocytes.

    Federica Barutta, Shunsuke Kimura, Koji Hase, Stefania Bellini, Beatrice Corbetta, Alessandro Corbelli, Fabio Fiordaliso, Antonella Barreca, Mauro Giulio Papotti, Gian Marco Ghiggeri, Gennaro Salvidio, Dario Roccatello, Valentina Audrito, Silvia Deaglio, Roberto Gambino, Stefania Bruno, Giovanni Camussi, Miriam Martini, Emilio Hirsch, Marilena Durazzo, Hiroshi Ohno, Gabriella Gruden

    Journal of the American Society of Nephrology : JASN 32 ( 5 ) 1114 - 1130 2021.03

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1046-6673

     View Summary

    BACKGROUND: Podocyte dysfunction and loss are major determinants in the development of proteinuria. FSGS is one of the most common causes of proteinuria, but the mechanisms leading to podocyte injury or conferring protection against FSGS remain poorly understood. The cytosolic protein M-Sec has been involved in the formation of tunneling nanotubes (TNTs), membrane channels that transiently connect cells and allow intercellular organelle transfer. Whether podocytes express M-Sec is unknown and the potential relevance of the M-Sec-TNT system in FSGS has not been explored. METHODS: We studied the role of the M-Sec-TNT system in cultured podocytes exposed to Adriamycin and in BALB/c M-Sec knockout mice. We also assessed M-Sec expression in both kidney biopsies from patients with FSGS and in experimental FSGS (Adriamycin-induced nephropathy). RESULTS: Podocytes can form TNTs in a M-Sec-dependent manner. Consistent with the notion that the M-Sec-TNT system is cytoprotective, podocytes overexpressed M-Sec in both human and experimental FSGS. Moreover, M-Sec deletion resulted in podocyte injury, with mitochondrial abnormalities and development of progressive FSGS. In vitro, M-Sec deletion abolished TNT-mediated mitochondria transfer between podocytes and altered mitochondrial bioenergetics. Re-expression of M-Sec reestablishes TNT formation and mitochondria exchange, rescued mitochondrial function, and partially reverted podocyte injury. CONCLUSIONS: These findings indicate that the M-Sec-TNT system plays an important protective role in the glomeruli by rescuing podocytes via mitochondrial horizontal transfer. M-Sec may represent a promising therapeutic target in FSGS, and evidence that podocytes can be rescued via TNT-mediated horizontal transfer may open new avenues of research.

  • Involvement of BMP and Wnt Signals Leadingto Epithelial-Mesenchymal Transition in Colon Adenocarcinoma with Heterotopic Ossification.

    Naho Katono, Masumi Tsuda, Jun Suzuka, Yoshitaka Oda, Lei Wang, Zen-Ichi Tanei, Mishie Tanino, Takanobu Ohata, Eisuke Nagabuchi, Yusuke Ishida, Shunsuke Kimura, Toshihiko Iwanaga, Shinya Tanaka

    Annals of clinical and laboratory science 51 ( 2 ) 271 - 276 2021.03

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0091-7370

     View Summary

    Here we present the case of a 73-year-old male with rectal adenocarcinoma with heterotopic ossification (HO). Cancer-associated HO in the digestive system is rare. Thus, the precise mechanism and clinicopathological significance of HO have not yet been defined. To clarify the molecular mechanisms of HO, we analyzed the expression levels of signaling molecules related to epithelial-mesenchymal transition (EMT) that lead to ossification in the tumor cells discriminating the ossified area (HO-area) and non-ossified area (non-HO area). Expression levels of BMP4 were elevated in both areas, whereas BMP2 was specifically increased in the HO-area by qPCR. EMT-related molecules such as Snail and Slug were especially higher in the HO-area. By immunohistochemistry, the expression of Smad4, nuclear staining of β-catenin, and the phosphorylated form of GSK-3β were detectable in both areas, and GSK-3β was highly phosphorylated in the HO-area. The tumor growth rate was extremely high, with the Ki-67 labeling index at 90%. In the HO-area, osteoblasts with alkaline phosphatase expression were distributed surrounding the tumor cells. This is the first demonstration of the involvement of EMT in HO of colon cancer through BMP/SMAD and WNT/β-catenin signaling pathways, which are especially prominent in the HO-area leading to the osteogenic property.

  • Characterization of M Cells in Tear Duct-Associated Lymphoid Tissue of Mice: A Potential Role in Immunosurveillance on the Ocular Surface.

    Yuki Oya, Shunsuke Kimura, Yutaka Nakamura, Narumi Ishihara, Shunsuke Takano, Ryo Morita, Mayumi Endo, Koji Hase

    Frontiers in immunology 12   779709 - 779709 2021

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    The ocular mucosal tissues are exposed to potentially harmful foreign antigens in the air and tear fluid. The tear duct-associated lymphoid tissue (TALT) may contribute to immune surveillance in the eye region. Follicle-associated epithelium (FAE) of TALTs is classified as stratified squamous epithelium and consists of squamous epithelial cells arranged in layers on the basement membrane. In contrast, most mucosa-associated lymphoid tissue is covered by a monolayer of epithelium containing microfold (M) cells. Therefore, antigen uptake and the presence of M cells in TALT are not fully understood. The present study found that a small population of FAE cells in the TALT expressed intestinal M-cell markers, namely Sox8, Tnfaip2, GP2, and OPG. This cell population was identified as functional M cells because of their uptake capacity of luminal nanoparticles. In addition, RANKL, which is essential for M-cell differentiation, was expressed by stroma-like cells at the subepithelial region and its receptor RANK by the FAE in the TALT. The administration of RANKL markedly increased the number of Sox8+ M cells. In contrast, deficiency in OPG, an endogenous inhibitor of RANKL, increased the number of M cells in the TALT. These data demonstrate that the RANKL-RANK axis is essential for M-cell differentiation in the TALT. Furthermore, immunization via eye drops elicited the production of antigen-specific antibodies in tears, which was enhanced by RANKL administration. Thus, TALT M cells play an important role in the immunosurveillance of the eye region.

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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 article, 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 article, Joint Work,  ISSN  1881-1930

  • 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

  • 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 article, 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

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Presentations 【 Display / hide

  • RANKL-OPGバランスによる腸管恒常性維持

    木村 俊介

    第62回歯科基礎医学会学術大会, 2020.09, Symposium, Workshop, Panelist (nomination)

  • 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

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

  • 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

    2019.10
    -
    2022.03

    JST, 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

    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)

     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.

  • 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)

     View Summary

    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.

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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 Awards

  • 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: Awards of National Conference, Council and Symposium

  • 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: Awards of National Conference, Council and Symposium

  • 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: Awards of National Conference, Council and Symposium

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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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