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However, the mechanism of NLRP3 inflammasome activation still remains elusive. Here we provide evidence that AKT regulates NLRP3 inflammasome activation. Upon NLRP3 activation, AKT activity is inhibited by second stimulus\u2010induced reactive oxygen species. In contrast, AKT activation leads to NLRP3 inhibition and improved mitochondrial fitness. Mechanistically, AKT induces the phosphorylation of the DDX3X (DEAD\u2010box helicase 3, X\u2010linked), a recently identified NLRP3 inflammasome component, and impairs the interaction between DDX3X and NLRP3. Furthermore, an AKT agonist reduces NLRP3\u2010dependent inflammation in two <jats:italic>in\u00a0vivo<\/jats:italic> models of LPS\u2010induced sepsis and Alum\u2010induced peritonitis. Altogether, our study highlights an important role of AKT in controlling NLRP3 inflammasome activation.<\/jats:p>","DOI":"10.1002\/1873-3468.14175","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T13:49:53Z","timestamp":1628862593000},"page":"2447-2462","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["AKT controls NLRP3 inflammasome activation by inducing DDX3X phosphorylation"],"prefix":"10.1002","volume":"595","author":[{"given":"Xingchen","family":"Guo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology College of Life Sciences Wuhan University China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Hangzhou 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