| Project/Area Number |
11557037
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
内科学一般
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MIYASAKA Nobuyuki Tokyo Medical and Dental University, Department of Bioregulatory Medicine and Rheumatology, Professor, 大学院・医歯学総合研究科, 教授 (30157622)
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| Co-Investigator(Kenkyū-buntansha) |
TOTSUKA Tetsuya Novartis Pharma Inc. Study Group, Manager, 研究本部, マネージャー
KOIKE Ryuji Tokyo Medical and Dental University, Department of Bioregulatory Medicine and Rheumatology, Assistant Professor, 大学院・医歯学総合研究科, 助手 (50250220)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1999: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | oral tolerance / MAdCAM-1 / adjuvant arthritis / monoclonal antibody / adhesion molecule / gut-associated lymphoid tissues(GALT) / 慢性関節リウマチ / MAdCAM-1分子 / 関節炎 / 粘膜免疫 / ホーミング / GALT |
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| Research Abstract |
For the purpose of application of Oral torelance to therapy for autoimmune diseases, We studied the physiological roles of the adhesion molecule MAdCAM-1, which expresses specifically at gut-associated lymphoid tissues (GALT), for the induction of oral tolerance. We established several monoclonal antibodies against MAdCAM-1 of rat and estimated as a tool for the coming studies. In the immunohistochemical study using rat at various age, MAdCAM-1 is expressed at skin and thymus in the embryo and neonatal stage. MAdCAM-1 expression is not recognized at skin and thymus in the adult rat, which suggests that MAdCAM-1 might play an important role for the transmigration of lymphocytes at embryo and neonatal stage.
When we injected anti-MAdCAM-1 blocking antibody into the rat at the time to induce adjuvant arthritis, the onset of arthritis was made a little earlier. Moreover, the injection of this antibody tended to inhibit the induction of oral tolerance against adjuvant arthritis. Taken together, it is suggested that MAdCAM-1 pathway might Support the induction of oral tolerance. Although it is necessary to confirm the findings in this study, it may be effective for the induction of oral tolerance to strengthen the pathway including MAdCAM-1, for the purpose of application to clinical medicine. It is also necessary to proceed the basic research about the mechanisms of oral tolerance including MAdCAM-1 pathway.
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