{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:04:15Z","timestamp":1773155055120,"version":"3.50.1"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol. Commun."],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>Autoimmune hepatitis (AIH) is an inflammatory disease of the liver. Liver X receptors (LXRs), including the \u03b1 and \u03b2 isoforms, are previously known for their anti\u2010inflammatory activities. The goal of this study is to determine whether and how LXR plays a role in AIH. LXR\u03b1 gain\u2010of\u2010function and loss\u2010of\u2010function mouse models were used, in conjunction with the concanavalin A (ConA) model of T\u2010cell mediated hepatitis. We first showed that the hepatic expression of LXR\u03b1 was decreased in the ConA model of hepatitis and in human patients with AIH. In the ConA model, we were surprised to find that activation of LXR\u03b1 in the constitutively activated VP\u2010LXR\u03b1 whole\u2010body knock\u2010in (<jats:italic toggle=\"yes\">LXR\u03b1\u2010KI<\/jats:italic>) mice exacerbated ConA\u2010induced AIH, whereas the <jats:italic toggle=\"yes\">LXR\u03b1\u2212\/\u2212\n                           <\/jats:italic> mice showed attenuated ConA\u2010induced AIH. Interestingly, hepatocyte\u2010specific activation of LXR\u03b1 in the fatty acid binding protein\u2013VP\u2010LXR\u03b1 transgenic mice did not exacerbate ConA\u2010induced hepatitis. Mechanistically, the sensitizing effect of the <jats:italic toggle=\"yes\">LXR\u03b1\u2010KI<\/jats:italic> allele was invariant natural killer T (iNKT)\u2013cell dependent, because the sensitizing effect was abolished when the <jats:italic toggle=\"yes\">LXR\u03b1\u2010KI<\/jats:italic> allele was bred into the NKT\u2010deficient <jats:italic toggle=\"yes\">CD1d\u2212\/\u2212\n                           <\/jats:italic> background. In addition, LXR\u03b1\u2010enhanced ConA\u2010induced hepatitis was dependent on interferon gamma. In contrast, adoptive transfer of hepatic iNKT cells isolated from <jats:italic toggle=\"yes\">LXR\u03b1\u2010KI<\/jats:italic> mice was sufficient to sensitize <jats:italic toggle=\"yes\">CD1d\u2212\/\u2212\n                           <\/jats:italic> mice to ConA\u2010induced AIH. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Activation of LXR\u03b1 sensitizes mice to ConA\u2010induced AIH in iNKT and interferon gamma\u2013dependent manner. Our results suggest that LXR\u03b1 plays an important role in the development of AIH.<\/jats:p>","DOI":"10.1002\/hep4.1584","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T03:53:36Z","timestamp":1597290816000},"page":"1664-1679","source":"Crossref","is-referenced-by-count":10,"title":["Activation of Liver X Receptor \u03b1 Sensitizes Mice to T\u2010Cell Mediated Hepatitis"],"prefix":"10.1097","volume":"4","author":[{"given":"Li","family":"Gao","sequence":"first","affiliation":[{"name":"Center for Pharmacogenetics and Department of Pharmaceutical Sciences,University of Pittsburgh,Pittsburgh,PA,USA"},{"name":"Department of Gastroenterology,Peking University People's Hospital,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenetics and Department of Pharmaceutical Sciences,University of 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Pittsburgh,Pittsburgh,PA,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runzi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Immunology,University of Pittsburgh,Pittsburgh,PA,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung\u2010Chun","family":"Tung","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenetics and Department of Pharmaceutical Sciences,University of Pittsburgh,Pittsburgh,PA,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meishu","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenetics and Department of Pharmaceutical Sciences,University of Pittsburgh,Pittsburgh,PA,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songrong","family":"Ren","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenetics and Department of Pharmaceutical Sciences,University of 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