| Project/Area Number |
16390143
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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 | 一般 |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MATSUSHIMA Kouji The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50222427)
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| Co-Investigator(Kenkyū-buntansha) |
HAINO Makoto The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (30345045)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | chemokine / chemokine receptors / immunological synapse / T cell receptor / arthritis / Rap-1 / 関節リウマチ |
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| Research Abstract |
To disclose the novel function of chemokine receptors, the roles of CCR5 and CXCR3 in T cell receptor mediated signaling were in detail examined. The expression of CCR5 was first found to be induced by T cell receptor mediated activation, and CCR5 and its ligand RANTES granules were observed to be accumulated in the immunological synapse. The activation of CCR5 through TCR mediated signaling was proved by bioluminescence resonance energy transfer method (BRET) using CCR5-renilla and GFP-beta-arrestin. Next, The critical role of CCR5 and CXCR3 in T cell memory response was proved by using CCR5 and CXCR3 double knock out mice-derived T lymphocytes. Furthermore, The pivotal role of CCR5 but not CXCR3 in Type-II collagen induced arthritis was established using CCR5, CXCR3 single and double knock out mice. This result indicates that CCR5 could be a novel therapeutic target for rheumatoid arthritis.
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