干扰素基因刺激剂
刺
信号转导
发病机制
基因敲除
基因
干扰素
化学
Ⅰ型干扰素
免疫学
生物
细胞生物学
生物化学
先天免疫系统
免疫系统
航空航天工程
工程类
作者
Jiehua Wang,Min Dai,Yange Cui,Guojun Hou,Jun Deng,Xin Gao,Zhuojun Liao,Ya Liu,Yao Meng,Lingling Wu,Chao Yao,Yan Wang,Jie Qian,Qiang Guo,Huihua Ding,Bo Qu,Nan Shen
摘要
Objective Increasing evidence indicates that the cyclic GMP ‐ AMP synthase/stimulator of interferon genes ( cGAS / STING ) signaling pathway has a critical pathogenic role in systemic lupus erythematosus ( SLE ). Expression levels of the interferon (IFN)–inducible gene IFIT 3 are elevated in SLE patients. However, it is still not clear how IFIT 3 contributes to the pathogenesis of SLE . This study was undertaken to investigate the activation of the cGAS / STING signaling pathway in human SLE monocytes, and to determine how elevated expression of IFIT 3 could contribute to overactive cGAS / STING signaling in patients with SLE. Methods Monocytes from SLE patients or healthy controls were examined for activity of the cGAS / STING signaling pathway and expression levels of IFIT 3. Correlations between cGAS / STING signaling activity and SLE clinical features were analyzed. Gain‐ or loss‐of‐function experiments were used to determine the role of IFIT 3 in cGAS / STING signaling. Coimmunoprecipitation assays were used to identify the interaction between IFIT 3 and other proteins. Results The cGAS / STING signaling pathway was found to have enhanced activity in monocytes from SLE patients compared to healthy controls, as indicated by the higher expression of IFN β downstream. Levels of IFIT 3 were significantly elevated in human SLE monocytes, and this was positively correlated with the activity of the cGAS / STING signaling pathway. In vitro, the expression of VACV 70‐induced IFN β was reduced by knockdown of IFIT 3, whereas overexpression of IFIT 3 produced an opposite effect. Finally, IFIT 3 was found to interact with both STING and TANK ‐binding kinase 1. Conclusion These findings suggest that IFIT 3 is one of the genes that contributes to the overactive cGAS / STING signaling pathway in human SLE monocytes. IFIT 3 may therefore serve as a novel therapeutic target for blocking the production of type I IFN and other proinflammatory cytokines by the cGAS / STING signaling pathway in patients with SLE.
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