Semaphorin 7A is a negative regulator of T cell responses
Semaphorin 7A is a negative regulator of T cell responses
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DOI：
10.1016/j.immuni.2006.03.013
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发表时间：
2006-05-01
期刊：
影响因子：
32.4
通讯作者：
Medzhitov, Ruslan
中科院分区：
文献类型：
--
作者：
Czopik, Agnieszka K.;Bynoe, Margaret S.;Medzhitov, Ruslan
脑信号蛋白在轴突导向中起着重要作用，并且新出现的证据指出了几个脑信号蛋白家族成员在免疫系统中的不同功能。Semaphorin 7A（Sema7A）促进中枢神经系统中的轴突生长。在这里，我们发现Sema7A在T细胞活化和功能的负调控中也起着关键作用。缺乏Sema7A的T细胞表现出增强的稳态和抗原诱导的增殖反应。此外，自身反应性Sema7A缺陷型T细胞介导侵袭性自身免疫性疾病。Sema7A的缺陷导致缺陷性TCR下调和T细胞高反应性。这些结果证明了Sema7A在限制自身免疫反应中的重要作用，并增加了越来越多的证据表明免疫和神经系统使用共享的信号通路。
Semaphorins play an essential role in axonal guidance, and emerging evidence points to diverse functions of several Semaphorin family members in the immune system. Semaphorin 7A (Sema7A) promotes axonal growth in the central nervous system. Here, we show that Sema7A also plays a critical role in negative regulation of T cell activation and function. T cells deficient in Sema7A exhibit enhanced homeostatic and antigen-induced proliferative response. Moreover, autoreactive Sema7A-deficient T cells mediate aggressive autoimmune disease. The deficiency in Sema7A leads to defective TCR downmodulation and T cell hyperres-ponsiveness. These results demonstrate an important role of Sema7A in limiting autoimmune responses and add to growing evidence of shared signaling pathways used by the immune and nervous systems.