{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:51:32Z","timestamp":1791312692841,"version":"4.3.1"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":239,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>There is increasing interest in the role of T follicular helper (Tfh) cells in autoimmunity from the perspective of both their role in breach of tolerance and their effects on the natural history of disease progression. Indeed, the critical role of Tfh cells in autoimmunity is further highlighted based on their location in the germinal center (GC), a pathogenic hot spot for development of autoreactivity. To address the role of Tfh cells in primary biliary cirrhosis (PBC), we comprehensively evaluated the immunobiology of CXCR5<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> Tfh cells in 69 patients with PBC, including a nested subgroup of 16 autoimmune hepatitis (AIH) and 20 healthy controls (HC), followed for 1 year. We report herein several key observations. First, there was an increased frequency of circulating Tfh cells in patients with PBC compared to AIH (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.05) and HC (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.01). Second, the function of circulating Tfh cells from PBC patients, including interleukin (IL)\u201021 production (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.05), the ability to promote B\u2010cell maturation, and autoantibody production, were greater than HC. Third, the frequency of these cells was significantly decreased in ursodeoxycholic acid (UDCA) responders compared to UDCA\u2010treated nonresponders, in both cross\u2010sectional (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.023) and longitudinal studies (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.036), respectively. Indeed, similar increases of Tfh cells were noted in liver and spleen. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: These results significantly extend our understanding of lymphoid subpopulations in PBC and their relative role in disease expression. Our data also provide a novel biomarker for evaluation of the effectiveness of new therapeutic approaches. (H<jats:sc>epatology<\/jats:sc> 2015;61:627\u2010638)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.27306","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T15:35:01Z","timestamp":1405438501000},"page":"627-638","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":109,"title":["CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis"],"prefix":"10.1097","volume":"61","author":[{"given":"Lifeng","family":"Wang","sequence":"first","affiliation":[{"name":"Research Center for Biological Therapy,Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department for Non\u2010infectious Diseases,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy,Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqiong","family":"Jia","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy,Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengsheng","family":"Zou","sequence":"additional","affiliation":[{"name":"Department for Non\u2010infectious Diseases,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbiao","family":"Ding","sequence":"additional","affiliation":[{"name":"Medical Affairs Department,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy,Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangsheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy,Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Jin","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy,Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy,Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department for Hepatobiliary Surgery,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Sun","sequence":"additional","affiliation":[{"name":"Research Center for Liver Transplantation,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy,Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa","family":"Lv","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy,Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy,Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baosen","family":"Li","sequence":"additional","affiliation":[{"name":"Department for Non\u2010infectious Diseases,Beijing 302 Hospital,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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