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Inappropriate activation of STING signaling can trigger excessive inflammation response to aggravate hepatic I\/R injury. Dimethyl fumarate (DMF) is an FDA\u2010approved immunomodulatory drug used to treat multiple sclerosis and psoriasis due to its notable anti\u2010inflammation properties. However, the mechanism and targets of DMF in immunomodulation remain unclear. Here, we found that DMF suppresses cGAS\u2010STING activation induced by HSV\u20101, hering testis DNA, and mitochondrial DNA in a variety of cells. DMF significantly reduces hepatic I\/R injury and inhibits cGAS\u2010STING pathway activation in mice. The alleviating effect of DMF on hepatic I\/R injury was negligible in STING\u2010knockout mice. Mechanistically, DMF directly inhibits STING activation via an autophagy\u2010independent pathway, and the immunocoprecipitation experiment showed that DMF inhibited STING recruitment of downstream TBK1 and IRF3. Our study found that DMF protects liver I\/R injury by inhibiting the STING pathway and may be a potential target of this disease.<\/jats:p>","DOI":"10.1002\/mco2.70077","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T11:52:59Z","timestamp":1738065179000},"source":"Crossref","is-referenced-by-count":15,"title":["Dimethyl fumarate alleviate hepatic ischemia\u2013reperfusion injury through suppressing cGAS\u2010STING signaling"],"prefix":"10.1002","volume":"6","author":[{"given":"Yi","family":"Xiong","sequence":"first","affiliation":[{"name":"Biotherapy Center The Third Affiliated Hospital of Sun Yat\u2010sen University Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Chen","sequence":"additional","affiliation":[{"name":"Biotherapy Center The Third Affiliated Hospital of Sun Yat\u2010sen University Guangzhou Guangdong P. R. 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