多发性硬化疾病及模型小鼠中疾病相关细胞因子和转录因子研究进展

Chemokines and Transcription Factors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

多发性硬化症(multiple sclerosis,MS)是一种原发于中枢神经系统的炎症性脱髓鞘疾病。实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)与MS有相似的临床症状和病理特征,是被广泛应用于人类疾病研究的动物模型。MS确切的发病机制尚不清楚,但普遍认为是在易感基因的基础上,受环境因素触发,由CD4+T细胞介导的中枢神经系统(centralnervous system,CNS)自身免疫性疾病。初始CD4+T细胞在T细胞受体介导下活化,继而可分化为至少4个主要亚型,分别为TH1、TH2、TH17和iTreg细胞,参与不同类型的免疫应答。细胞因子和转录因子网络对CD4+T细胞分化和效应细胞因子产物有重要意义。该文综述了各相关细胞因子和转录因子在CD4+T细胞向不同亚型分化及MS/EAE发病过程中的相互作用和调控,揭示各因子在这些过程中的作用,有助于进一步研究和治疗MS。

Multiple sclerosis （MS） is a demyelinating inflammatory disorder of the central nervous system. The experimental autoimmune encephalomyelitis （EAE） shares clinical and pathological features with MS and is widely used as the animal model for MS. The Pathogenesis of MS is still unknown, but it is widely accepted that MS is a CD4^＋ T cell-mediated autoimmune disease of the central nervous system which is based on susceptibility genes and triggered by environmental factors. Upon T-cell receptor （TCR）-mediated cell activation, naive CD4^＋ T cells can differentiate into at least four major lineages, TH1, TH2, TH17 and iTreg cells, which participate in different types of immune responses. Networks of cytokines and transcription factors are critical for CD4^＋ T cell differentiation and effector cytokine production. This article will review the collaboration and cross-regulation between various essential cytokines and transcription factors during the process of CD4^＋ T cell differentiation towards distinct lineages, as well as in the process of MS/EAE. Understanding the roles of key cytokines and transcription factors in these processes will help to understand disease pathogenesis and supply indications for disease therapy.