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Expression levels of the interferon (IFN)\u2013inducible gene IFIT<\/jats:styled-content>3 are elevated in SLE<\/jats:styled-content> patients. However, it is still not clear how IFIT<\/jats:styled-content>3 contributes to the pathogenesis of SLE<\/jats:styled-content>. This study was undertaken to investigate the activation of the cGAS<\/jats:styled-content>\/STING<\/jats:styled-content> signaling pathway in human SLE<\/jats:styled-content> monocytes, and to determine how elevated expression of IFIT<\/jats:styled-content>3 could contribute to overactive cGAS<\/jats:styled-content>\/STING<\/jats:styled-content> signaling in patients with SLE.<\/jats:p><\/jats:sec>Methods<\/jats:title>Monocytes from SLE<\/jats:styled-content> patients or healthy controls were examined for activity of the cGAS<\/jats:styled-content>\/STING<\/jats:styled-content> signaling pathway and expression levels of IFIT<\/jats:styled-content>3. Correlations between cGAS<\/jats:styled-content>\/STING<\/jats:styled-content> signaling activity and SLE<\/jats:styled-content> clinical features were analyzed. Gain\u2010 or loss\u2010of\u2010function experiments were used to determine the role of IFIT<\/jats:styled-content>3 in cGAS<\/jats:styled-content>\/STING<\/jats:styled-content> signaling. Coimmunoprecipitation assays were used to identify the interaction between IFIT<\/jats:styled-content>3 and other proteins.<\/jats:p><\/jats:sec>Results<\/jats:title>The cGAS<\/jats:styled-content>\/STING<\/jats:styled-content> signaling pathway was found to have enhanced activity in monocytes from SLE<\/jats:styled-content> patients compared to healthy controls, as indicated by the higher expression of IFN<\/jats:styled-content>\u03b2 downstream. Levels of IFIT<\/jats:styled-content>3 were significantly elevated in human SLE<\/jats:styled-content> monocytes, and this was positively correlated with the activity of the cGAS<\/jats:styled-content>\/STING<\/jats:styled-content> signaling pathway. In vitro, the expression of VACV<\/jats:styled-content>70\u2010induced IFN<\/jats:styled-content>\u03b2 was reduced by knockdown of IFIT<\/jats:styled-content>3, whereas overexpression of IFIT<\/jats:styled-content>3 produced an opposite effect. Finally, IFIT<\/jats:styled-content>3 was found to interact with both STING<\/jats:styled-content> and TANK<\/jats:styled-content>\u2010binding kinase 1.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>These findings suggest that IFIT<\/jats:styled-content>3 is one of the genes that contributes to the overactive cGAS<\/jats:styled-content>\/STING<\/jats:styled-content> signaling pathway in human SLE<\/jats:styled-content> monocytes. IFIT<\/jats:styled-content>3 may therefore serve as a novel therapeutic target for blocking the production of type I IFN<\/jats:styled-content> and other proinflammatory cytokines by the cGAS<\/jats:styled-content>\/STING<\/jats:styled-content> signaling pathway in patients with SLE.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40576","type":"journal-article","created":{"date-parts":[[2018,5,28]],"date-time":"2018-05-28T01:34:44Z","timestamp":1527471284000},"page":"2036-2045","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Association of Abnormal Elevations in IFIT<\/scp>3 With Overactive Cyclic GMP<\/scp>\u2010AMP<\/scp> Synthase\/Stimulator of Interferon Genes Signaling in Human Systemic Lupus Erythematosus Monocytes"],"prefix":"10.1002","volume":"70","author":[{"given":"Jiehua","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Institute of Rheumatology Renji Hospital School of Medicine Shanghai 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