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


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

  • Inhibition of RANKL and Sema4D improves residual ridge resorption in mice.

    Meri Hisamoto, Shunsuke Kimura, Kai Iwata, Toshihiko Iwanaga, Atsuro Yokoyama

    Scientific reports 12 ( 1 ) 4094 - 4094 2022.03

    Corresponding author, Accepted

     View Summary

    Residual ridge resorption (RRR) is a chronic and progressive bone resorption following tooth loss. It causes deterioration of the oral environments and leads to the pathogenesis of various systemic diseases. However, the molecular mechanisms and risk factors for RRR progression are still unclear and controversial. In this study, we developed a tooth extraction model using mice for analyzing long-term morphological and gene expression changes in the alveolar bone. We further applied ovariectomy to this model to elucidate the effects of osteoporosis on RRR progression. As a result, the alveolar bone loss was biphasic and consisted of rapid loss in the early stages and subsequently slow and sustained bone loss over a long period. Histological analysis indicated that ovariectomy prolonged the activation of osteoclasts in the alveolar bone. Furthermore, the expressions of Tnfsf11 and Sema4d kept increasing for a long time in OVX mice. Administration of neutralization antibodies for receptor activator of NF-κB ligand (RANKL) effectively suppressed RRR. Similarly, inhibition of Semaphorin 4D (Sema4D) also improved alveolar bone loss. This study demonstrated that reduced ovarian function may be a risk factor for RRR and that RANKL and Sema4D suppression are potential treatments.

  • 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

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    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

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    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.

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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

  • 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

  • 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, 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



    Symposium, workshop panel (nominated)

  • 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




    Symposium, workshop panel (nominated)

  • M細胞による抗原の取り込みと粘膜免疫系の制御





  • 粘膜免疫の最前線で働くM細胞の歴史と最近の知見





  • 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, 



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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


    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

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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.

  • 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.

  • Host-microbe interaction mediated by intestinal M cells


    The University of Tokyo, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Hase Koji, MIMURO Hitomi, FURUSAWA Yukihiro, KIMURA Shunsuke, Grant-in-Aid for Scientific Research (B), No Setting

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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.

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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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