趋化因子CXCL10(IP-10)/CXCR3在类风湿关节炎发病中的作用及应用前景

摘要

类风湿关节炎(RA)是一类以关节炎为主要临床表现的系统性自身免疫性疾病.实验证明,T细胞尤其是CD4+T细胞的异常活化及其分泌的细胞因子所形成的网络参与了RA激发和延续.趋化因子在炎症细胞向滑膜组织迁移及活化过程中发挥了关键作用,趋化因子C-X-C配体10/干扰素诱导蛋白-10(CXCL10/IP-10)可与表达在T细胞表面的受体趋化因子C-X-C受体3(CXCR3)结合促进其活化并向CD4+ Th1细胞方向分化,从而促进炎症反应.研究发现,CXCL10在RA血清及滑膜中表达增高.目前作为RA的一个可能的致病因素,CXCL10/CXCR3在发病机制中的作用越来越受到重视.研究发现,CXCL10抗体及裸DNA疫苗可对RA关节炎有抑制及治疗作用,其可能作为RA治疗新靶点的研究日益增多.%Rheumatoid arthritis(RA) is one of the systemic autoimmune diseases, which mainly manifests as arthritis. It has been proved that the abnormal activation of T lymphocytes, especially CD4+ T cells, and the cytokines secreted by them are involved in the initiation and progression of RA. Chemokines play a key role in the activation and migration of inflammatory cells to synovial tissue. C-X-C ligands 10/interferon-inducible protein-10(CXCL10/IP-10) could bind its receptor CXCR3 on the surface of T cells, induce the activation of T cells and the differentiation into CD4+Th1 cells, and thereby promote the inflammatory reaction. Moreover, it was found that CXCL10 was highly expressed in the serum and synovium of patients with RA. Currently, as a possible pathogen, CXCL10/CXCR3 is drawing more and more attention in the pathogenesis of RA. Since accumulating evidence indicated that antibodies and naked DNA vaccine of CXCL10 could inhibit and treat RA, CXCL10 may be used as a new target for the treatment of RA.