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A spontaneous severe murine model of autoimmune liver disease has been previously established in dnTGF\u03b2RII Aire\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, exhibiting disease phenotypes that resemble both human primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). The data suggests that auto\u2010reactive liver\u2010specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells are the primary pathogenic cells in liver injury. In this study, these data are advanced through the use of both single\u2010cell sequencing and extensive in vitro analysis. The results identify a specific expanded pathogenic subset of PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the liver, exhibiting strong functional activity and cytotoxicity against target cells. Depletion of PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells using CAR\u2010T cells effectively alleviates the disease. GSDMD\u2010mediated pyroptosis is found to be aberrantly activated in the livers of model mice, and treatment with a GSDMD\u2010specific inhibitor significantly inhibits disease progression. In vitro experiments reveal that PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells can induce the pyroptosis of hepatocytes through elevated production of granzyme B and perforin\u20101. These results provide a novel explanation for the cytotoxic activity of pathogenic liver PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in autoimmune liver diseases and offer potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1002\/advs.202407284","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T05:10:24Z","timestamp":1730697024000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["PD\u20101\n                    <sup>+<\/sup>\n                    CD8\n                    <sup>+<\/sup>\n                    T Cell\u2010Mediated Hepatocyte Pyroptosis Promotes Progression of Murine Autoimmune Liver Disease"],"prefix":"10.1002","volume":"12","author":[{"given":"Jie","family":"Long","sequence":"first","affiliation":[{"name":"Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen\u2010Hua","family":"Bian","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Engineering South China University of Technology Guangzhou International Campus  Guangzhou 511442 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Xian","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou 510006 China"},{"name":"Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou 510006 China"},{"name":"Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weici","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology University of California Davis  Davis CA 95616 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases Air Force Military Medical University  Xi'an 710000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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