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2002 Fiscal Year Final Research Report Summary

Establishment of a novel therapy of Inflammatory bowel disease by inducible oral tolerance

Research Project

Project/Area Number 13670498
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 University, Department of Gastroenterology and Hepatology, Instructor, 医学部附属病院, 助手 (40245478)

Co-Investigator(Kenkyū-buntansha) YAGITA Hideo  Juntendo University School of Medicine, Department of Immunology, Assistant professor, 医学部, 助教授 (30182306)
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)
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)
Project Period (FY) 2001 – 2002
Keywordsinflammatory bowel disease / therapy / mucosal immunity / oral tolerance / commensal bacteria / IgA / chronic colitis / costimulation
Research Abstract

For years medical researchers have strived to develop selective immunotherapies that could specifically ameliorate pathogenic immune responses without immunocompromising the patient. Blockade of many known receptors on T cells can inhibit the initiation of immune responses. However, this approach is problematic in that it is not possible to predict the onset of disease in patients. Current immunotherapies are unsatisfactory for sporadic exacerbating-type of diseases such as multiple sclerosis and inflammatory bowel disease (IBD), because they require either long-term treatment or acute treatment with high-dose immunosuppressants. With regard to this issue, the inducible and inflammatory site-specific molecule, inducible co-stimulator (ICOS), may be particularly useful as an ideal targeting molecule for the strategy of treatment of human IBD patients. First, we found significantly increased expression of ICOS on T cells in inflamed colon from both IBD patients and colitic mice, but not in uninflamed mucosa and in periphery. Based on these results, we demonstrated anti-ICOS mAb ameliorated chronic murine experimental colitis when administrated either early or late after induction of colitis. In addition, we are under investigation to establish a bacterium genetically enginneered to secrete soluble costimulatory molecules to inhibit physiological costimulatory pathway for a novel therapy of IBD.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Totsuka T, Kanai T, et al.: "Ameliorating Effect of Anti-Inducible Costimulator Monoclonal Antibody in a Murine Model of Chronic Colitis"Gastroenterology. 124. 410-421 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Totsuka T, Kanai T, et al.: "Therapeutic effect of anti-OX40L and anti-TNF-a in a murine model of chronic colitis"Am J Physiol. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okamoto R, Kanai T, Watanabe M, et al.: "Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract"Nature Med. 8. 1011-1017 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanai T, Watanabe M, et al.: "ICOS costimulation in inflammatory bowel disease"J Gastroenterol. 37. S37-S41 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamazaki T, Azuma M, Yagita H, et al.: "Expression od programmed death 1 ligands by murine T cells and APC"J Immunol. 169. 5538-5545 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 金井隆典, 渡辺 守: "Annual Review 消化器"中外医学社. 238-248 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Totsuka T, Kanai T, Iiyama R, Uraushihara K, Yamazaki M, Okamoto R, Hibi T, Tezuka K, Azuma M, Akiba H, Yagita H, Okumura K. Watanahe M.: "Ameliorating Effect of Anti-Inducible Costimulator Monoclonal Antibody in a Murine Model of Chronic Colitis"Gastroenterology. 124. 410-421 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Totsuka T, Kanai T, et al: "Therapeutic effect of anti-OX40L and anti-TNF-a in a murine model of chronic colitis"Am J Physiol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okamoto R, Yajima T, Yamazaki M, Kanai T, Mukai M, Okamoto S, Ikeda Y, Hibi T, Inazawa J, Watanabe M.: "Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract"Nature Med 8. 1011-1017 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanai T, Totsuka T, tezuka K, Watanabe M.: "ICOS costimulation in inflammatory bowel disease"J Gastroenterol. 37. 78-81 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y, Shin T, Tsuchiya H, Pardoll DM, Okumura K, Azuma M, Yagita H: "Expression of programmed death 1 ligands by murine T cells and APC"J Immunol. 169. 5538-5545 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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