期刊
CLINICAL IMMUNOLOGY
卷 136, 期 2, 页码 197-204出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2010.03.428
关键词
CD4(+) T cell; FTY720; Rheumatoid arthritis; SKG mouse
类别
资金
- Ministry of Education, Science and Culture of Japan [20790701]
- Grants-in-Aid for Scientific Research [20790701] Funding Source: KAKEN
We investigated the effects and mechanisms by which FTY720 (FTY) inhibits arthritis development in the SKG mouse rheumatoid arthritis (RA) model. FTY (1 mg/kg/day) administration suppressed the progression of laminarin-induced arthritis in SKG mice. FTY treatment decreased IL-6 and TNF-alpha expression in synovial fibroblast cells and the number of inflammatory cells overall. Bone destruction was also suppressed by treatment with FTY. The numbers of CD4(+) and CD8(+) T cells were significantly increased in the thymus and decreased in the spleen in FTY-treated SKG mice. FTY enhanced IL-4 production by CD4(+) T cells stimulated by allogeneic spleen cells and inhibited prostaglandin E-2 (PGE(2)) production by a TNF-alpha-stimulated synovial fibroblast cell line. These results indicate that FTY can inhibit arthritis in SKG mice via sequestration of autoimmune CD4(+) T cells in the thymus, enhancement of Th2 immune responses, and inhibition of PGE(2) production by synovial cells. (C) 2010 Elsevier Inc. All rights reserved.
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