Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis
Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis
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DOI：
10.1172/jci12563
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发表时间：
2001-09-01
影响因子：
15.9
通讯作者：
Khoury, SJ
中科院分区：
文献类型：
--
作者：
Chitnis, T;Najafian, N;Khoury, SJ
实验性自身免疫性脑脊髓炎(EAE)是由分泌Th1细胞因子的髓鞘特异性CD4(+)T细胞介导的，而疾病的恢复与Th2细胞因子的表达有关。对单个细胞因子在疾病诱发中的作用的研究得出了相互矛盾的结果。在这里，我们使用靶向缺失STAT4或STAT6基因的动物来确定这些信号分子在EAR中的作用。STAT4途径控制细胞分化为Th1表型，而STAT6途径控制细胞分化为Th2表型。我们发现，STAT4基因缺陷的小鼠对EAE的诱导具有抵抗力，XVIth中枢神经系统中最低限度的炎性浸润。相反，与野生型或STAT4基因敲除小鼠相比，具有主要Th1表型的STAT6缺陷小鼠经历了更严重的EAE临床病程。此外，采用转移研究证实了体内Th2环境的调节功能。这些新的数据表明，STAT4和STAT6基因在调节EAE的自身免疫反应中起着关键作用。
Experimental autoimmune encephalomyelitis (EAE) is mediated by myelin-specific CD4(+) T cells secreting Th1 cytokines, while recovery from disease is associated with expression of Th2 cytokines. Investigations into the role of individual cytokines in disease induction have yielded contradictory results. Here we used animals with targeted deletion of the STAT4 or STAT6 genes to determine the role of these signaling molecules in EAR The STAT4 pathway controls the differentiation of cells into a Th1 phenotype, while the STAT6 pathway controls the differentiation of cells into a Th2 phenotype. We found that mice deficient in STAT4 are resistant to the induction of EAE, xvith minimal inflammatory infiltrates in the central nervous system. In contrast, STAT6-deficient mice, which have a predominantly Th1 phenotype, experience a more severe clinical course of EAE as compared with wild-type or STAT4 knockout mice. In addition, adoptive transfer studies confirm the regulatory functions of a Th2 environment in vivo. These novel data indicate that STAT4 and STAT6 genes play a critical role in regulating the autoimmune response in EAE.