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

作　　者：苏蓉慧 程丽云 字晓宇 王会 李小峰[1] 王彩虹[1] Su Ronghui;Cheng Liyun;Zi Xiaoyu;Wang Hui;Li Xiaofeng;Wang Caihong(Department of Rheumatology and Immunology,the Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第二医院风湿免疫科,太原030001

出　　处：《中华微生物学和免疫学杂志》2024年第5期460-467,共8页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金(81971543);山西省重点研发计划(社会发展领域)(201803D31119);山西省"四个一批"科技兴医创新计划项目重大科技攻关(2022XM05)。

摘　　要：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.

关 键 词：cGAS-STING信号通路 类风湿关节炎 Ⅰ型干扰素 胞质DNA感受器 

分 类 号：R593.22[医药卫生—内科学]