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2003 Fiscal Year Final Research Report Summary

Elucidation of the regulatory mechanisms for mucosal immune response by mucosal IL-7/IL-7 receptor system

Research Project

Project/Area Number 14570453
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NAKAMURA Tetsuya  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Instructor, 大学院・医歯学総合研究科, 助手 (70265809)

Co-Investigator(Kenkyū-buntansha) AZUMA Miyuki  Tokyo Medical and Dental University, Department of Molecular Immunology, Professor, 大学院・医歯学総合研究科, 教授 (90255654)
KANAI Takanori  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Assistant Professor, 医学部附属病院, 講師 (40245478)
WATANABE Mamoru  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Professor, 大学院・医歯学総合研究科, 教授 (10175127)
TSUBATA Takeshi  Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (80197756)
ISHIKAWA Hiromichi  Keio University, School of Medicine, Microbiology and Immunology, Professor, 医学部, 教授 (20051667)
Project Period (FY) 2002 – 2003
KeywordsIL-7 / IL-7 receptor / mucosal immunity / intestinal epithelial cell / transcriptional regulation / chronic colitis / IRF-1 / IRF-2
Research Abstract

Our group has been focusing on the fundamental roles of intestinal epithelial cell-derived IL-7 and IL-7R-expressing lymphoid cells in local immune regulation within the gut. In this project, further attempts were made 1) to elucidate the regulatory mechanisms of IL-7 production in intestinal epithe-hal cells, and 2) to test whether elimination of IL-7R-expressing cells by toxin-conjugated anti-IL-7R antibodies might influence the pathogenesis of chronic colitis. We showed 1) that gene expression and protein production of JL-7 in intestinal epithelial cells are elegantly regulated by IRF family of tran-scription factors and also 2) that direct immunotoxin targeting of IL-7R caused significant ameliora-tion of chronic colitis in several model mice. These results not only provide a better understanding of the molecular mechanisms of mucosal immune regulation, but also propose the mucosal IL-7/IL-7R system to be a potential therapeutic target for a certain type of chronic colitis in humans.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Nakamura T, Tanaka H, et al.: "Cytokine receptor common beta subunit-mediated STAT5 activation confers NF-kappaB activation in murine proB cell line Ba/F3 cells"J Biol Chem. 277. 6254-6265 (2002)

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  • [Publications] Uraushihara K, Nakamura T, et al.: "Regulation of murine inflammatroy bowel disease by CD25+ and CD25- CD4+ glucocorticoid-induced TNF receptor family-related gene+ regulatory T cells"J Immunol. 171. 708-716 (2003)

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      「研究成果報告書概要(和文)」より
  • [Publications] Yamazaki M, Nakamura T, et al.: "Mucosal T Cells Expressing High Levels of IL-7 Receptor Are Potential Targets for Treatment of Chronic Colitis."J Immunol. 171. 1556-1563 (2003)

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  • [Publications] Kanai T, Nakamura T, et al.: "Blockade of B7-H1 suppresses the development of chronic intestinal inflammation."J Immunol. 171. 4156-4163 (2003)

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      「研究成果報告書概要(和文)」より
  • [Publications] Ohshima S, Nakamura T, et al.: "IRF-1 and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells."Mol Cell Biol. (in press). (2004)

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  • [Publications] Nakamura T, Ouchida R, Kodama T, Kawashima T, Makino Y, Yoshikawa N, Watanabe S, Morimoto C, Kitamura T, Tanaka H: "Cytokine receptor common beta subunit-mediated STATS activation confers NIF-kappaB activation in murine proB cell line BafF3 cells."J Biol Chem. 277. 6254-6265 (2002)

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  • [Publications] Watanabe S, Murakaini T, Nakamura T, Morimoto C, Arai K: "Human GM-CSF induces HIV-1 LTR by multiple signaling pathways."Biochimie. 84. 633-642 (2002)

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  • [Publications] Kanai T, Iiyama R, Ishikura T, Uraushihara K, Totsuka T, Yamazaki M, Nakamura T, Watanabe M: "Role of innate immune system in the development of chronic colitis."J Gastroenterol. 37. 38-42 (2002)

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  • [Publications] Iiyama R, Kanai T, Uraushihara K, Totsuka T, Nakamura T, Miyata T, Yagita H, Tezuka K, Watanabe M: "The role of Inducible Co-stimulator (ICOS)/B7 related protein-1 (B7RP-1) interaction in the germinal center formation in Peyer's patches."Immunol Letters. 88. 62-70 (2003)

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  • [Publications] Ishikura T, Kanai T, Uraushihara K, Iiyama R, Makita S, Totsuka T, Yamazaki M, Sawada T, Nakamura T, Kitahora T, Hibi T, Watanabe M: "IL-18 overexpression exacerbates the development of colitis with marked infiltrating macrophages in IL-18 transgenic mice."J Gastol Hepatol. 18. 960-969 (2003)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Uraushihara K, Kanai T, Ko K, Totsuka T, Makita S, Iiyama R, Nakamura T, Watanabe M: "Regulation of murine inflammatory bowel disease by CD25+ and CD25-CD4+ glucocorticoid-induced TNF receptor family-related gene regulatory T cells."J Immunol.. 171. 708-716 (2003)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Yamazaki M, Yajima T, Tanabe M, Fukui K, Okada E, Okamoto R, Oshima S, Nakamura T, Kanai T, Takeuchi T, Uehira M, Ishikawa H, Hibi T, Watanabe M: "Mucosal T Cells Expressing High Levels of IL-7 Receptor Are Potential Targets for Treatment of Chronic Colitis."J Immunol. 171. 1556-1563 (2003)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Makita S, Kanai T, Matsumoto S, Iiyama R, Uraushihara K, Totsuka T, Yamazaki M, Nakamura T, Ishikawa H, Watanabe M: "The role of cryptopatch-derived intraepithelial lymphocytes in the development of chronic ileocecitis."Scand J Immunol.. 58. 428-435 (2003)

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  • [Publications] Kanai T, Totsuka T, Uraushihara K, Makita S, Nakamura T, Koganei K, Fukushima T, Akiba H, Yagita H, Okumura K, Machida U, Iwai H, Azuma M, Chen L, Watanabe M: "Blockade of B7-H 1 suppresses the development of chronic intestinal inflammation."J Immunol.. 171. 4156-4163 (2003)

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  • [Publications] Iiyama R, Kanai T, Uraushihara K, Ishikura T, Makita S, Totsuka T, Yamazaki M, Nakamura T, Miyata T, Yoshida H, Takeuchi O, Hoshino K, Takeda K, Ishikawa H, Akira S, Watanabe M: "Normal development of the gut-associated lymphoid tissue except Peyer's patch in MyD88-deficient mice."Scand J Immunol.. 58. 620-627 (2003)

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  • [Publications] Ishii K, Kanai T, Totsuka T, Uraushihara K, Ishikura T, Yamazaki M, Okamoto R, Araki A, Miyata T, Tezuka K, Nakamura T, Watanabe M: "Hyperexpression of inducible costimulator on lamina propria mononuclear cells in rat dextran sulfate sodium colitis."J Castroenterol Hepatol.. 19. 174-181 (2004)

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  • [Publications] Kawamura T, Kanai T, Dohi T, Uraushihara K, Totsuka T, Iiyama R, Taneda C, Yamazaki M, Nakamura T, Higuchi T, Aiba Y, Tsubata T, Watanabe M: "Ectopic CD4O Ligand Expression on B Cells Triggers Intestinal Inflammation."J Immunol.. 172. 6388-6397 (2004)

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  • [Publications] Nakamura T, Oshima S, Namiki S, Okada E, Tsuchiya K, Okamoto R, Yamazaki M, Yokota T, Aida M, Yamaguchi Y, Kanai T, Handa H, Watanabe M: "Interferon Regulatory Factor-1 (IRE-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells."Mol Cell Biol.. (in press). (2004)

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Published: 2005-04-19  

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