| Project/Area Number |
13470107
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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 |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MORIMOTO Chikao The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (30119028)
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| Co-Investigator(Kenkyū-buntansha) |
HOSONO Osamu The University of Tokyo, The Institute of Medical Science, Assistant Professor, 医科学研究所, 助手 (50190210)
WATANABE Sumiko The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (60240735)
TANAKA Hirotoshi The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (00171794)
KAWASAKI Hiroshi The University of Tokyo, The Institute of Medical Science, Assistant Professor, 医科学研究所, 助手 (80280957)
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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 |
¥16,300,000 (Direct Cost: ¥16,300,000)
Fiscal Year 2002: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2001: ¥11,500,000 (Direct Cost: ¥11,500,000)
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| Keywords | β1 integrin / signal molecule / Cas-L / Rheumatoid Arthritis / tax transgenic mice / Fyn / lck / tyrosine phosphorylation / T細胞 / CD45RAナイーブ / CD45ROメモリー / CD9 / 共刺激 / アポトーシス / 自己抗原 / β2GPI |
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| Research Abstract |
It has been repeated that the expression of b1 integrins and ligands are elevated in the inflammatory lesions in rheumatoid arthritis (RA), Crk-associated substrate lymphocyte type (Cas-L) is a docking protein that is heavily tyrosine phosphorylated by the engagement of β1 integrins in T cells.
In the present study, we attempted to evaluate the role of Cas-L in the pathophysiology of rheumatoid arthritis (RA). We analyzed human T-lymphotropic virus type I (HTLV-I) tax transgenic mice, since they develop polyarthritis resembling human RA. Here we show that migratory activity of spleen cells from tax transgenic mice with arthritis (Atg) was much higher than that of tax transgenic mice without arthritis (Ntg) and littermate control mice (Ct). Biochemical studies revealed that Cas-L protein and its spontaneous tyrosine phosphorylation were increased in Atg mice compared to Ntg and Ct mice, which might be caused by activated fyn and lck. Immunohistochemical analysis showed a large number of Cas-L positive lymphocytes migrating into the affected joints. Finally, in human RA, Cas-L positive lymphocytes have been shown to infiltrate to the inflammatory lesions. The above results strongly suggest that Cas-L appears to play an important role in the pathophysiology of RA.
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