{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:18:02Z","timestamp":1784308682265,"version":"3.55.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"9","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A3B207889011"],"award-info":[{"award-number":["2020R1A3B207889011"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019H1A2A1074484"],"award-info":[{"award-number":["2019H1A2A1074484"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,2,28]]},"abstract":"<jats:p>\n                    Liver X receptor (LXR) is a critical regulator of cholesterol homeostasis that inhibits T cell receptor (TCR)-induced proliferation by altering intracellular sterol metabolism. However, the mechanisms by which LXR regulates helper T cell subset differentiation remain unclear. Here, we demonstrate that LXR is a crucial negative regulator of follicular helper T (Tfh) cells in\u00a0vivo. Both mixed bone marrow chimera and antigen-specific T cell adoptive cotransfer studies show a specific increase in Tfh cells among LXR\u03b2-deficient CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell population in response to immunization and lymphocytic choriomeningitis mammarenavirus (LCMV) infection. Mechanistically, LXR\u03b2-deficient Tfh cells express augmented levels of T cell factor 1 (TCF-1) but comparable levels of Bcl6, CXCR5, and PD-1 in comparison with those of LXR\u03b2-sufficient Tfh cells. Loss of LXR\u03b2 confers inactivation of GSK3\u03b2 induced by either AKT\/Extracellular signal-regulated kinase (ERK) activation or Wnt\/\u03b2-catenin pathway, leading to elevated TCF-1 expression in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells. Conversely, ligation of LXR represses TCF-1 expression and Tfh cell differentiation in both murine and human CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells. LXR agonist significantly diminishes Tfh cells and the levels of antigen-specific IgG upon immunization. These findings unveil a cell-intrinsic regulatory function of LXR in Tfh cell differentiation via the GSK3\u03b2-TCF1 pathway, which may serve as a promising target for pharmacological intervention in Tfh-mediated diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2213793120","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T13:58:31Z","timestamp":1676987911000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":11,"title":["Liver X receptor controls follicular helper T cell differentiation via repression of TCF-1"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0537-838X","authenticated-orcid":false,"given":"Jiyeon","family":"Kim","sequence":"first","affiliation":[{"name":"Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea"},{"name":"Brain Korea 21 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