| Project/Area Number |
13670498
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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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)
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| 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)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | inflammatory bowel disease / therapy / mucosal immunity / oral tolerance / commensal bacteria / IgA / chronic colitis / costimulation / OX40 |
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| 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.
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