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Establishment of transgenic mice that recognize bacteria specific antigen and develop spontaneous colitis under specific pathogen free condition.

Research Project

Project/Area Number 15590627
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

KANAI Takanori  Tokyo Medical and Dental Univ., Dept.of Gastroenteorology and Hepatology, Assistant professor, 医学部・附属病院, 講師 (40245478)

Co-Investigator(Kenkyū-buntansha) WATANABE Mamoru  Tokyo Medical and Dental Univ., Dept.of Gastroenteorology and Hepatology, Professor, 大学院・医歯学総合研究科, 教授 (10175127)
YAGITA Hideo  Juntendo Univ., Dept.of Immunology, 医学部, 助教授 (30182306)
HIBI Toshifumi  Keio Univ., Dept.of Internal Medicine, 医学部, 教授 (50129623)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsinflammatory bowel diseases / murine model / Antigen-specific / Crohn's disease / Ulcerative colitis / Probiotics / Cell transfer / Transgenic mice / 調節性T細胞 / 慢性大腸炎 / 調節製T細胞 / 腸管粘膜免疫 / 単クローン / 慢性大腸炎モデル / 自然免疫 / 腸内細菌 / 自己免疫疾患
Research Abstract

In this study, we clarified that intestinal bacteria flora is essential for the development of chronic colitis using murine model of chronic colitis. We in general used adoptive transfer model that normal CD4+CD45RBhigh T cells from spleens are transferred into SCID mice. This model has the strong advadvantages that we can exactly evaluate the pathogenic T cells in clonal level.
We are now under investigation to establish bacteria-specidfic antigen recognizing TCR transgenic mouse after the isolation of TCRab genes. Using this model, we believe that we can brake through to understand the exact mechanism of action in terms of antigen-specific analysis. Furthermore, we will find out a new strategy using probiotics for the treatment of inflammatory bowel diseases.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (45 results)

All 2005 2004 2003 Other

All Journal Article (38 results) Book (1 results) Publications (6 results)

  • [Journal Article] MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis.2005

    • Author(s)
      Araki A, Kanai T, et al.
    • Journal Title

      J Gastroenterol 40

      Pages: 16-23

    • NAID

      10014370953

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] IL-7 exacerbates chronic colitis with expansion of memory IL-7R^<high>CD4^+ mucosal T cells in mice.2005

    • Author(s)
      Okada E, Yamazaki M, Tanabe M, Takeuchi T, Nanno M, Oshima S, Okamoto R, Tsuchiya K, Nakamura T, Kanai T, Hibi T, Watanabe M.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 288

      Pages: 745-754

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis.2005

    • Author(s)
      Araki A, Kanai T, Ishikura T, Makita S, Uraushihara K, Iiyama R, Totsuka T, Takeda K, Akira S, Watanabe M.
    • Journal Title

      J Gastroenterol 40

      Pages: 16-23

    • NAID

      10014370953

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical significance of microsatellite instability in the inflamed mucosa for the prediction of colonic neoplasms in patients with ulcerative colitis.2005

    • Author(s)
      Tahara T, Inoue N, Hisamatsu T, Kashiwagi K, Takaishi H, Kanai T, Watanabe M, Ishii H, Hibi T.
    • Journal Title

      J Gastrornt Hepatol 20

      Pages: 710-715

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ectopic CD40 ligand expression on B cells triggers intestinal inflammation.2004

    • Author(s)
      Kawamura T, Kanai T, et al.
    • Journal Title

      J Immunol 172

      Pages: 6388-6397

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hyperexpression of inducible costimulator and its contribution on lamina propria T cells in inflammatory bowel disease.2004

    • Author(s)
      Sato T, Kanai T, et al.
    • Journal Title

      Gastroenterology 126

      Pages: 829-839

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Blockade of B7-H1 suppresses the development of chronic intestinal inflammation.2004

    • Author(s)
      Kanai T, et al.
    • Journal Title

      J Immunol 171

      Pages: 4156-4163

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of IL-7 in human intestinal epithelial cells.2004

    • Author(s)
      Oshima S, Kanai T, et al.
    • Journal Title

      Mol Cell Biol 24

      Pages: 6298-6310

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] CD4^+CD25^<bright>FoxP3^+ regulatory T cells in human intestinal lamina propria.2004

    • Author(s)
      Makita S, Kanai T, et al.
    • Journal Title

      J Immunol 173

      Pages: 3119-3130

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human intestinal epithelia-derived IL-18 is a potent prolifrerative factor for intraepithelial lymphocytes synergistically with IL-2, IL-7 and IL-15.2004

    • Author(s)
      Okazawa A, Kanai T, Nakamaru T, Sato T, Inoue N, Ogata H, Iwao Y, Ikeda M, Kawamura T, Makita S, Uraushihara K, Okamoto R, Yamazaki M, Kurimoto M, Ishii H, Watanabe M, Hibi T.
    • Journal Title

      Clin Exp Immunol 136

      Pages: 269-276

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hyperexpression of inducible costimulator and its contribution on lamina propria T cells in inflammatory bowel disease.2004

    • Author(s)
      Sato T, Kanai T, Watanabe M, Sakuraba A, Okamoto S, Nakai T, Okazawa A, Inoue N, Totsuka T, Yamazaki M, Kroczek RA, Fukushima T, Ishii H, Hibi T.
    • Journal Title

      Gastroenterology 126

      Pages: 829-839

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] T-bet up-regulation and subsequent interleukin 12 stimulation are essential for the induction of Th1 mediated immunopathology in Crohn's disease.2004

    • Author(s)
      Matsuoka K, Inoue N, Sato T, Okamoto S, Hisamatsu T, Kishi Y, Atsushi Sakuraba A, Hitotsumatsu O, Fukushima T, Kanai T, Watanabe M, Ishii H, Hibi T.
    • Journal Title

      Gut 53

      Pages: 1303-1308

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ectopic CD40 ligand expression on B cells triggers intestinal inflammation.2004

    • Author(s)
      Kawamura T, Kanai T, Dohi T, Uraushihara K, Totsuka T, Iiyama R, Taneda C, Yamazaki M, Nakamura T, Aiba Y, Tsubata T, Watanabe M.
    • Journal Title

      J Immunol 172

      Pages: 6388-6397

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hepatitis C virus infection in human liver tissue engrafted in mice with an infectious molecular clone.2004

    • Author(s)
      Maeda N, Watanabe M, Okamoto S, Kanai T, Yamada T, Hata J, Hozumi N, Katsume A, Nuriya H, Sandhu J, Ishii H, Kohara M, Hibi T.
    • Journal Title

      Liver Int 24

      Pages: 259-267

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively upregulate gene expression and production of interleukin-7 in human intestinal epithelial cells.2004

    • Author(s)
      Oshima S, Nakamura T, Kanai T, Handa H, Watanabe M.
    • Journal Title

      Mol Cell Biol 24

      Pages: 6298-6310

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] CD4^+CD25^<bright>FoxP3^+ regulatory T cells in human intestinal lamina propria.2004

    • Author(s)
      Makita S, Kanai T, Oshima S, Uraushihara K, Totsuka T, Iiyama R, Sawada T, Nakamura T, Koganei K, Fukushima T, Watanabe M.
    • Journal Title

      J Immunol 173

      Pages: 3119-3130

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] CD4^+CD25^<bright>FoxP3^+ regulatory T cells in human intestinal lamina propria.2004

    • Author(s)
      Makita S, Kanai T, et al.
    • Journal Title

      J Immunology 173

      Pages: 3119-3130

    • Related Report
      2004 Annual Research Report
  • [Journal Article] IRF-1 and IRF-2 distinctively up-regulate gene expression and production of IL-7 in human intestinal epithelial cells.2004

    • Author(s)
      OshimaS, Kanai T, et al.
    • Journal Title

      Mol Cell Biol 24

      Pages: 6298-6310

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hyperexpression of inducible costimulator and its contribution on amina propria T cells in inflammatory bowel disease.2004

    • Author(s)
      Sato T, Kanai T, et al.
    • Journal Title

      Gastroenterology 126

      Pages: 829-839

    • Related Report
      2004 Annual Research Report
  • [Journal Article] T-bet up-regulation and subsequent interleukin 12 stimulation are essential for the induction of Thl mediated immunopathology in Crohn's disease.2004

    • Author(s)
      Matsuoka K, Kanai T, et al.
    • Journal Title

      Gut 53

      Pages: 1303-1308

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human intestinal epithelia-derived IL-18 is a potent prolifrerative factor or intraepithelial lymphocytes synergistically with IL-2,IL-7 and IL-15.2004

    • Author(s)
      Okazawa A, Kanai T, et al.
    • Journal Title

      Clin Exp Immunol 1362

      Pages: 269-276

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ameliorating effect of anti-ICOS monoclonal antibody in a murine model of chronic colitis.2003

    • Author(s)
      Totsuka T, Kanai T^#, Iiyama R, Uraushihara K, Yamazaki M, Okamoto R, Hibi T, Tezuka K, Azuma M, Akiba H, Yagita H, Okumura K, Watanabe M.
    • Journal Title

      Gastroenterology 124

      Pages: 410-421

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Preventive and therapeutic effects of chronic colitis in CD4^+CD45RB^+ T cell-transferred SCID mice by anti-OX40L mAb administration.2003

    • Author(s)
      Totsuka T, Kanai T^#, Uraushihara K, Iiyama R, Akiba H, Yagita H, Okumura K, Watanabe M.
    • Journal Title

      Am J Physiol GI & Liver 284

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A specific genetic alteration on chromosome 6 in ulcerative colitis-associated colorectal cancers.2003

    • Author(s)
      Ezaki, Watanabe M, Inoue N, Kanai T^#, Ogata H, Iwao Y, Ishii H, Hibi T.
    • Journal Title

      Cancer Res 63

      Pages: 3747-3749

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of inducible co-stimulator (ICOS)/B7 related protein-1 (B7RP-1) interaction in the functional development of Peyer's patches.2003

    • Author(s)
      Iiyama R, Kanai T^#, Uraushihara K, Totsuka T, Nakamura T, Miyata T, Yagita H, Kushi A, Suzuki K, Tezuka K, Watanabe M.
    • Journal Title

      Immunol Letters 88

      Pages: 63-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of murine inflammatory bowel disease by CD25^+ and CD25^-CD4^+ Glucocorticoid-induced TNF receptor family-related gene^+ regulatory T cells.2003

    • Author(s)
      Uraushihara K^*, Kanai T^<*, #>, Ko K, Totsuka T, Makita S, Iiyama R, Nakamura T, Watanabe M.
    • Journal Title

      J Immunol 171

      Pages: 708-716

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] IL-18 overexpression exacerbates the development of colitis with marked infiltrates macrophages in IL-18 transgenic mice.2003

    • Author(s)
      Ishikura T, Kanai T^#, Uraushihara K, Iiyama R, Makita S, Totsuka T, Yamazaki M, Sawada T, Nakamura T, Kitahora T, Hibi T, Hoshino T, Watanabe M.
    • Journal Title

      J Gastroenterol Hepatol 18

      Pages: 960-969

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulfate (DSS) colitis in mice.2003

    • Author(s)
      Takagi H, Kanai T, Okazawa A, Kishi Y, Sato T, Takaishi H, Inoue N, Ogata H, Iwao Y, Hoshino K, Takeda K, Akira S, Ishii H, Watanabe M, Hibi T.
    • Journal Title

      Scan J Gastroenterol 33

      Pages: 837-844

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Preventive effects of chronic colitis in CD4^+CD45RB^+ T cell-transferred SCID mice by anti-FasL mAb administration.2003

    • Author(s)
      Dan N, Kanai T, Totsuka T, Iiyama R, Yamazaki M, Sawada T, Miyata T, Yagita H, Okumura K, Watanabe M.
    • Journal Title

      Am J Physiol GI & Liver 285

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of cryptopatch-derived intraepithelial lymphocytes in the development of chronic ileocaetitis.2003

    • Author(s)
      Makita S, Kanai T, Matsumoto S, Iiyama R, Uraushihara K, Totsuka T, Yamazaki M, Nakamura T, Ishikawa H, Watanabe M.
    • Journal Title

      Scan J Immunol 58

      Pages: 428-435

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hyperexpression of inducible costimulator (ICOS) on lamina propria mononuclear cells in rat dextran sulfate sodium (DSS).2003

    • Author(s)
      Ishii K, Kanai T, Ishikura T, Totsuka T, Uraushihara K, Yamazaki M, Okamoto R, Araki A, Ohka S, Miyata T, Nakamura T, Kitahora T, Hibi T, Tezuka K, Watanabe M.
    • Journal Title

      J Gastroenterol Hepatol 19

      Pages: 174-181

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis.2003

    • Author(s)
      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.
    • Journal Title

      J Immunol 171

      Pages: 1556-1563

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Blockade of B7-H1 suppresses the development of chronic intestinal inflammation.2003

    • Author(s)
      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.
    • Journal Title

      J Immunol 171

      Pages: 4156-4163

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Morphological and functional abnormalities of Peyer's patch in MyD88-deficient mice.2003

    • Author(s)
      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.
    • Journal Title

      Scan J Immunol 58

      Pages: 620-627

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine.

    • Author(s)
      Matsumoto T, Okamoto R, Yagima T, Mori T, Okamoto S, Ikeda Y, Yamazaki M, Oshima S, Tsuchiya K, Nakamura T, Kanai T, Okano H, Inazawa J, Hibi T, Watanabe M.
    • Journal Title

      Gastroenterology (in the press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis.

    • Author(s)
      Kanai T^#, Uraushihara K, Totsuka T, Nemoto Y, Fujii R, kawamura T, Makita S, Yagita H, Okumura K, Watanabe M.
    • Journal Title

      J Gastrornt Hepatol (in the press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of murine chronic colitis by CD4^+CD25^-Programed Death-1^+ T cells.

    • Author(s)
      Totsuka T, Kanai T, Makita S, Fujii R, Nemoto Y, Oshima S, Okamoto R, Koyanagi A, Akiba H, Okumura K, Yagita H, Watanabe M.
    • Journal Title

      Eur J Immunol (in the press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] IRF-inducing proteosomes in human intestinal epithelial cells.

    • Author(s)
      Namiki S, Nakamura T, Oshima S, Tsuchiya K, Kanai T, Watanabe M.
    • Journal Title

      FEBES J (in the press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 外科2004

    • Author(s)
      岡田英理子, 金井隆典, 渡辺守
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Totsuka T, Kanai T, et al.: "Ameliorating effect of anti-inducible co-stimulator monoclonal antibody in a murine model of chronic colitis."Gastroenterology. 124. 410-421 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ezaki T, Kanai T, et at.: "A specific genetic alteration on chromosome 6 in ulcerative colitis-associated colorectal cancers."Cancer Res. 63. 3747-3749 (2003)

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

    • Related Report
      2003 Annual Research Report
  • [Publications] Yanazaki M, Kanai T, et al.: "Mucosal T cells exoressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis."J Immunol. 171. 1556-1563 (2003)

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

    • Related Report
      2003 Annual Research Report
  • [Publications] Dan N, Kanai T, et al.: "Preventive effects of chronic colitis in CD4^+CD45RB^+T cell-transferred SCID mice by anti-FasL mAb administration."Am J Physiol GI & Liver. 285. 754-760 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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