TNF-α在类风湿关节炎患者外周血Th17/Treg细胞平衡中的作用

The role of TNF-α in the Th17/Treg cell balance of peripheral blood in patients with rheumatoid arthritis

类风湿关节炎(rheumatoid arthritis,RA)是一种以慢性滑膜炎症、进行性骨质破坏为主要临床表现的自身免疫性疾病,由于淋巴细胞不断浸润及活化,引起关节滑膜组织异常增殖,造成关节畸形及功能障碍。RA发病率高、致残率高、病死率高、分布范围广,患者年龄跨度大,由于其病因与发病机制尚不明确,给临床治疗带来一定困难。近年人们发现辅助性T细胞17(T helper cell 17,Th17)的促炎作用与调节性T细胞(regulatory T cell,Treg)的抑炎作用在RA发病过程中发挥重要作用,Th17/Treg细胞平衡与RA的关系越来越受到人们重视。Th17、Treg细胞均由初始CD4+T细胞受到外来抗原刺激后活化形成,二者分化发育相互制约,在各种致炎、抗炎因子相互作用下,当Th17细胞比例增多则功能亢进,Treg细胞比例减少则功能低下,最终发生Th17/Treg平衡失调,加重RA病程发展,出现滑膜炎症、关节破坏及骨侵蚀等症状。肿瘤坏死因子-α(TNF-α)由巨噬细胞、T细胞和NK细胞在某些刺激因子作用下分泌,在调节免疫细胞及促进炎症反应方面发挥重要作用,参与RA病程进展。TNF-α可通过抑制Treg细胞合成调节Th17/Treg细胞平衡。干预TNF-α成为治疗RA的新研究方向,近年其拮抗剂治疗RA取得了一定成果。本研究通过查阅国内外文献综述TNF-α、Th17/Treg细胞平衡与RA的研究进展,为干预TNF-α表达治疗RA奠定理论基础。

Rheumatoid arthritis(RA)is a kind of autoimmune disease with chronic synovial inflammation and progressive bone destruction as its main clinical manifestations.Because of the continuous infiltration and activation of lymphocytes,it causes abnormal proliferation of synovial tissue,resulting in joint deformity and dysfunction.RA has high incidence rate,high disability rate,high mortality and wide distribution,and the age span of patients is wide.Because its etiology and pathogenesis are not clear,it brings some difficulties to clinical treatment.In recent years,it has been found that the pro-inflammatory effect of T helper cell 17(Th17)and antiinflammatory effect of regulatory T cell(Treg)play an important role in the pathogenesis of RA,so that more and more attention has been paid to the relationship between Th17/Treg cell balance and RA.Th17 and Treg cells are activated and formed by the initial CD4+T cells stimulated by foreign antigens,and their differentiation and development are mutually restricted.Under the interaction of various inflammatory and anti-inflammatory factors,when the proportion of Th17 cells increases,their functions will be hyperactive;when the proportion of Treg cells decreases,their functions will be low.Finally,Th17/Treg imbalance will occur,which will aggravate the course of RA,resulting in synovial inflammation,joint destruction and bone invasion erosion and other symptoms.Tumor necrosis factorα(TNF-α)is secreted by macrophages,T cells and NK cells under the action of some stimulating factors.It plays an important role in regulating immune cells and promoting inflammatory response,and participates in the progression of RA.TNF-αcan regulate Th17/Treg cell balance by inhibiting Treg cell synthesis.Intervention of TNF-αhas become a new research direction in the treatment of RA,and in recent years,its antagonists have made some achievements in the treatment of RA.This article reviewed the research progress of TNF-α,Th17/Treg cell balance and RA by referring to the literatures at home and abroad,so as to lay a theoretical foundation for the intervention of TNF-αexpression in the treatment of RA.