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The liver orchestrates systemic bile acid (BA) metabolism, a pathway disrupted in chronic liver diseases such as viral hepatitis. BAs are increasingly recognized for their immunomodulatory properties. Thus, improved understanding of the interplay between immunity and BA metabolism may reveal novel therapeutic avenues. Using lymphocytic choriomeningitis virus (LCMV) as a model, we investigated the interplay between chronic virus infection, BA metabolism, and immunity. Chronic LCMV infection increased BA levels and shifted circulating and liver BA composition toward host-derived, conjugated BAs. Hepatic BA transport and synthesis genes were broadly downregulated, in part depending on CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Pharmacological inhibition of the main hepatic transporter of conjugated BAs, NTCP (\n                    <jats:italic>Slc10a1<\/jats:italic>\n                    ), increased hepatic damage, while combined genetic disruption of the BA transporters\n                    <jats:italic>Slco1a1<\/jats:italic>\n                    ,\n                    <jats:italic>Slco1a4<\/jats:italic>\n                    , and\n                    <jats:italic>Slco1b2<\/jats:italic>\n                    , responsible for the hepatic reuptake of unconjugated BA, reduced liver pathology and impaired antiviral CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses. These findings reveal a reciprocal interplay between BA metabolism and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, expanding our understanding of adaptive immunity in viral hepatitis. They also highlight how immunometabolic changes in liver disease may affect adaptive immune responses against infections.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.189882","type":"journal-article","created":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T18:01:02Z","timestamp":1782064862000},"source":"Crossref","is-referenced-by-count":0,"title":["Crosstalk between CD8+ T cells and systemic bile acid metabolism shapes antiviral immunity and immunopathology"],"prefix":"10.1172","volume":"11","author":[{"given":"Felix Clemens","family":"Richter","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria."},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsofia","family":"Keszei","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria."},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csilla","family":"Viczenczova","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria."},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique G.","family":"Cola\u00e7o","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria."},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Siller","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria."},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Holnsteiner","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatoon","family":"Baazim","sequence":"additional","affiliation":[{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria."},{"name":"Sabri \u00dclker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. 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