Involvement of Sema4A in the progression of experimental autoimmune myocarditis
Involvement of Sema4A in the progression of experimental autoimmune myocarditis
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DOI：
10.1016/j.febslet.2008.10.040
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发表时间：
2008-11-26
期刊：
影响因子：
3.5
通讯作者：
Kumanogoh, Atsushi
中科院分区：
文献类型：
--
作者：
Makino, Nobuhiko;Toyofuku, Toshihiko;Kumanogoh, Atsushi
扩张型心肌病常由心肌炎时微生物感染引发的自身免疫引起。然而，免疫紊乱如何参与自身免疫性心肌炎的发病机制仍不清楚。在这里，我们证明了Sema 4A，IV类信号蛋白，在实验性自身免疫性心肌炎（EAM）中起着关键作用。树突状细胞脉冲与肌球蛋白重链-a肽诱导严重的心肌炎野生型小鼠，但不是在Sema 4A缺陷小鼠。在过继转移实验中，来自野生型小鼠的CD 4（+）T细胞诱导了严重的心肌炎，而来自Sema 4A缺陷小鼠的CD 4（+）T细胞表现出相当弱的心肌炎。我们的研究结果表明，Sema 4A是通过调节T细胞的分化在EAM中至关重要。(C)2008年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Dilated cardiomyopathy often results from autoimmunity triggered by microbial infections during myocarditis. However, it remains unclear how immunological disorders are implicated in pathogenesis of autoimmune myocarditis. Here, we demonstrated that Sema4A, a class IV semaphorin, plays key roles in experimental autoimmune myocarditis (EAM). Dendritic cells pulsed with myosin heavy chain-a peptides induced severe myocarditis in wild-type mice, but not in Sema4A-deficient mice. In adoptive transfer experiments, CD4(+) T-cells from wildtype mice induced severe myocarditis, while CD4(+) T-cells from Sema4A-deficient mice exhibited considerably attenuated myocarditis. Our results indicated that Sema4A is critically involved in EAM by regulating differentiation of T-cells. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.