Makino Nobuhiko, Toyofuku Toshihiko, Takegahara Noriko, Takamatsu Hyota, Okuno Tatsusada, Nakagawa Yukinobu, Kang Sujin, Nojima Satoshi, Hori Masatsugu, Kikutani Hitoshi, Kumanogoh Atsushi
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
FEBS Lett. 2008 Nov 26;582(28):3935-40. doi: 10.1016/j.febslet.2008.10.040. Epub 2008 Oct 31.
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-alpha peptides induced severe myocarditis in wild-type mice, but not in Sema4A-deficient mice. In adoptive transfer experiments, CD4+ T-cells from wild-type 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.
扩张型心肌病通常由心肌炎期间微生物感染引发的自身免疫所致。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。在此，我们证明了IV类信号素Sema4A在实验性自身免疫性心肌炎（EAM）中起关键作用。用肌球蛋白重链α肽脉冲处理的树突状细胞在野生型小鼠中可诱发严重心肌炎，但在Sema4A缺陷型小鼠中则不会。在过继转移实验中，来自野生型小鼠的CD4 + T细胞诱发了严重心肌炎，而来自Sema4A缺陷型小鼠的CD4 + T细胞所诱发的心肌炎则明显减轻。我们的结果表明，Sema4A通过调节T细胞分化而在EAM中起关键作用。
