cGAS-STING信号通路:类风湿关节炎的潜在治疗靶点

The cGAS-STING pathway:a potential therapeutic target for rheumatoid arthritis

环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子(cyclic GMP-AMP synthase-stimulator of interferon gene,cGAS-STING)信号通路作为固有免疫系统的重要组成部分,是胞质DNA识别的主要途径,cGAS可由多种胞质双链DNA触发,成为连接自身免疫、无菌炎症反应和细胞衰老的重要桥梁。近年来,cGAS-STING通路在自身免疫性疾病中越来越受到关注。在类风湿关节炎(rheumatoid arthritis,RA)中,中性粒细胞胞外陷阱(neutrophil extracellular traps,NETs)通过cGAS-STING通路引发Ⅰ型干扰素反应、加速抗瓜氨酸化蛋白抗体(anti-citrullinated peptide antibody,ACPA)产生;此外,cGAS-STING通路还通过促进成纤维细胞样滑膜细胞增殖活化、M1型巨噬细胞极化参与滑膜炎及骨破坏,参与RA的发生发展。抑制cGAS-STING通路或其下游信号通路可以减少RA的滑膜炎症,cGAS-STING通路可能是RA的潜在治疗靶点。

Cyclic GMP-AMP synthase(cGAS)-stimulator of interferon gene(STING)pathway,as an important part of the innate immune system,is the main pathway for cytoplasmic DNA recognition and cGAS can be triggered by a variety of cytoplasmic dsDNA.This pathway has become an important bridge connecting autoimmunity,aseptic inflammatory response and cell aging.In recent years,cGAS-STING pathway has attracted increasing attention in autoimmune diseases.In rheumatoid arthritis(RA),neutrophil extracellular traps(NETs)induce typeⅠinterferon response and accelerate the production of anti-citrullinated peptide antibody(ACPA)through the cGAS-STING pathway.In addition,the cGAS-STING pathway also participates in synovitis,bone destruction and RA progression by promoting the proliferation and activation of fibroblast-like synovitis cells and the polarization of M1 macrophages.Inhibition of the cGAS-STING pathway or its downstream signaling pathway can reduce synovial inflammation in RA,suggesting that cGAS-STING pathway may be a potential therapeutic target for RA.