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Here, we use Il12b\n                    <jats:sup>-\/-<\/jats:sup>\n                    Il2ra\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that\n                    <jats:italic>Cd8a<\/jats:italic>\n                    knockout or treatment with an anti-CD8\u03b1 antibody prevents\/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8\n                    <jats:sup>+<\/jats:sup>\n                    tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8\n                    <jats:sup>+<\/jats:sup>\n                    Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8\n                    <jats:sup>+<\/jats:sup>\n                    Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8\n                    <jats:sup>+<\/jats:sup>\n                    Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8\n                    <jats:sup>+<\/jats:sup>\n                    Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-46654-5","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T02:02:01Z","timestamp":1712282521000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Targeting pathogenic CD8+ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3363-7983","authenticated-orcid":false,"given":"Hao-Xian","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1715-0416","authenticated-orcid":false,"given":"Shu-Han","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai-Yue","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Hua","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Min","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Rong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Li","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haosheng","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Tsuneyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3046-9507","authenticated-orcid":false,"given":"Ying","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-2571","authenticated-orcid":false,"given":"Liang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0691-2556","authenticated-orcid":false,"given":"Zhi-Bin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5245-2680","authenticated-orcid":false,"given":"M. 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