类风湿关节炎发生发展中TNF-α信号通路与CD4^+T细胞的关系

Relationship between TNF-α signaling pathway and the function of CD4+T cell subsets in rheumatoid arthritis

CD4+T细胞各亚群在类风湿关节炎(RA)的发生发展过程中发挥不同的作用。其中,辅助性T细胞1(Th1)/Th2细胞、Th17/调节性T细胞(Treg)细胞比例的失衡及细胞因子白细胞介素-1(IL-1)、IL-2、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)等产生的免疫损害,是导致RA慢性炎症的关键因素。TNF-α作为一种重要的促炎细胞因子在RA致病过程中起到了重要作用。TNF-α有两个受体,TNF受体1(TNF receptor 1,TNFR1)在大多数细胞上表达,而TNFR2仅在T细胞等免疫细胞上表达,调节T细胞的存活、活化和增殖。反之,T细胞对TNF-α信号通路也有影响。该文就RA的发病机制中TNF-α及其信号通路和CD4+T细胞各亚群功能的关系加以综述,为RA的防治提供新的思路。

CD4＋ T cell subsets play different roles in the patho- genesis of rheumatoid arthritis （RA）. The helper T （Thl）/Th2 and Thl7/regulatory T cells （Treg） imbalance and pro-inflamma- tory cytokines, such as interleukin-1 （ IL-1 ）, IL-2, interferon-γ （IFN-γ） and tumor necrosis factor-α（TNF-α）, are the key fac- tors in the chronic inflammation of RA. TNF-α interacts with two different receptors, designated TNF receptor 1 （TNFR1） and TNFR2, which are expressed in different cells and tissues. TN-FR1 is expressed in most cells. However, TNFR2 is only ex- pressed in T cells and other immune cells which regulate the sur- vival, activation and proliferation of T-lymphocytes. This review summarizes the relationship between TNF-α signaling pathway and the function of CD4＋ T cell subsets in the pathogenesis of RA in an attempt to provide new ideas for the treatment of RA.