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Inflammation driven by immune cells has been linked to liver damage, fibrosis, and the progression of MASH. Here, single\u2010cell transcriptome analysis disclosed the increasing hepatic infiltration of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in a murine methionine\u2010 and choline\u2010deficient (MCD) diet\u2010induced MASH model. Simvastatin alleviated the progression of MCD\u2010diet\u2010induced MASH, accompanied by the decreased infiltration of T cells. Depletion of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells also improved MASH progression. It is widely recognized that cholesterol plays an indispensable role in tuning the activation and function of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. We found that specific inhibition of cholesterol synthesis in T cells significantly reduced MCD\u2010induced hepatic steatosis, damage, inflammation, and concurrently lowered the accumulation of T cells and macrophages in the liver. Mechanistic studies revealed that MCD\u2010induced hepatic oxidative stress was reduced by inhibiting T\u2010cell cholesterol metabolism. Simvastatin ameliorated MASH in mice, at least in part through inhibiting the infiltration and effector function of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Collectively, our findings provide compelling evidence that pharmacological modulation of T\u2010cell cholesterol metabolism may represent a promising therapeutic approach in the treatment of MASH.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500115r","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T09:50:49Z","timestamp":1749203449000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of Cholesterol Synthesis in T Cells Protects the Liver Against Steatosis, Inflammation, and Oxidative Stress in Metabolic Dysfunction\u2010Associated Steatohepatitis"],"prefix":"10.1096","volume":"39","author":[{"given":"Huizhen","family":"Lin","sequence":"first","affiliation":[{"name":"Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) &amp; School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Pathology, the Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Biomedical Innovation Center, the Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwei","family":"Lin","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) &amp; 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