{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:16:21Z","timestamp":1768450581820,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T00:00:00Z","timestamp":1555891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009109","name":"Pharmaceuticals","doi-asserted-by":"publisher","award":["BH149474"],"award-info":[{"award-number":["BH149474"]}],"id":[{"id":"10.13039\/501100009109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. Approximately 30% of patients do not respond to therapy with ursodeoxycholic acid (UDCA). Previous studies have implicated increased senescence of cholangiocytes in patients who do not respond to UDCA. This may increase the release of cytokines which drive pathogenic T cell polarization. As FXR agonists are beneficial in treating UDCA non\u2010responsive patients, the current study was designed to model the interactions between cholangiocytes and CD4+ T cells to investigate potential immunomodulatory mechanisms of bile acid receptor agonists. Human cholangiocytes were co\u2010cultured with CD4+ T cells to model the biliary stress response. Senescent cholangiocytes were able to polarize T cells toward a Th17 phenotype and suppressed expression of FoxP3 (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.0043). Whilst FXR and TGR5 receptor agonists were unable directly to alter cholangiocyte cytokine expression, FGF19 was capable of significantly reducing IL\u20106 release (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.044). Bile acid receptor expression was assessed in PBC patients with well\u2010characterized responsiveness to UDCA therapy. A reduction in FXR staining was observed in both cholangiocytes and hepatocytes in PBC patients without adequate response to UDCA. Increased IL\u20106 expression by senescent cholangiocytes represents a potential mechanism by which biliary damage in PBC could contribute to excessive inflammation.\n                  <\/jats:p>","DOI":"10.1096\/fba.2018-00046","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T10:51:05Z","timestamp":1553511065000},"page":"332-343","source":"Crossref","is-referenced-by-count":14,"title":["Bile acid receptor agonists in primary biliary cholangitis: Regulation of the cholangiocyte secretome and downstream T cell differentiation"],"prefix":"10.1096","volume":"1","author":[{"given":"Rachel E.","family":"Etherington","sequence":"first","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin J. 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