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多发性硬化(multiple sclerosis,MS)是以中枢神经系统(central nervous system,CNS)慢性炎症性脱髓鞘为主要特征的自身免疫性疾病。实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)在发病特点和病理学特征上与人类的MS表现非常相似,是研究MS发病机制及治疗的理想的动物模型。辅助性T细胞17(T helper cell 17,Th17)细胞是CD4~+T细胞的一个重要亚群,主要分泌IL-17(interleukin-17)细胞因子,在EAE的发病过程中具有重要作用。NF-κB激活剂1(NF-κB activator 1,Act1)是SEFIR(similar expression to fibroblast growth factor genes/IL-17R)蛋白家族的一员,是IL-17信号通路的连接蛋白。在IL-17的刺激下,Act1通过SEFIR-SEFIR相互作用招募到IL-17受体(IL-17 receptor,IL-17R)上,以调节下游信号通路。对Act1介导的IL-17信号与自身免疫性疾病的关系做一综述,以期为EAE的发病机制研究和治疗提供重要的理论基础和分子靶标。
Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammatory demyelination of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is very similar to human MS in the pathogenesis and pathological features, and is an ideal animal model for studying the pathogenesis and treatment of MS. T helper cell 17 (Th17) cells are an important subpopulation of CD4 ~ + T cells and mainly secrete interleukin-17 (IL-17) cytokines, which play an important role in the pathogenesis of EAE. NF-κB activator 1 (Act1) is a member of the SEFIR protein family and is a connexin of the IL-17 signaling pathway. Act1 is recruited to the IL-17 receptor (IL-17R) through the SEFIR-SEFIR interaction to regulate downstream signaling pathways, stimulated by IL-17. This review summarizes the relationship between Act1-mediated IL-17 signaling and autoimmune diseases in order to provide an important theoretical basis and molecular targets for the study of the pathogenesis of EAE.