{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:15:27Z","timestamp":1783116927349,"version":"3.54.6"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K11105"],"award-info":[{"award-number":["24K11105"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K11145"],"award-info":[{"award-number":["24K11145"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJSP2109"],"award-info":[{"award-number":["JPMJSP2109"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Primary biliary cholangitis (PBC) is an autoimmune liver disease marked by progressive bile duct damage, leading to bile retention. Dendritic cells (DCs), as antigen\u2010presenting cells, are crucial for immune regulation, and their dysfunction is linked to autoimmunity. This study demonstrates that DC\u2010depleted mice manifest an autoimmune biliary disease resembling human PBC and investigates its mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>DC\u2010depleted mice were generated by crossbreeding CD11c\u2010Cre and Rosa26\u2010DTA (ID) mice. Hepatobiliary changes were assessed using hematoxylin and eosin staining, serum biochemistry, flow cytometry, and immunohistochemistry. Liver gene expression was analyzed using quantitative polymerase chain reaction (qPCR) and RNA sequencing. Antimitochondrial antibody (AMA) and IFN\u2010\u03b3 secretion were measured through enzyme\u2010linked immunosorbent assay. Wild\u2010type mice were intraperitoneally injected with serum from control mice (IP\u2010Ctrl) or ID mice (IP\u2010ID); in some experiments, anti\u2010PDCE\u20102\u2010depleted ID serum (IP\u2010\u0394PDCE2) was used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ID mice showed significant portal inflammation, with neutrophils and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\/CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes around bile ducts. Serum AMA levels in ID mice were 1.8\u2010fold higher than those of control mice. qPCR revealed higher expression of inflammatory molecules and cytokines (TNF\u2010\u03b1, IFN\u2010\u03b3, IL\u20102, IL\u201012p35, and N\u2010ras) in the liver of ID mice. IP\u2010ID mice developed cholangitis within 10\u00a0days, marked by CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell\u2010dominant infiltration, which was attenuated by depleting anti\u2010PDCE\u20102 antibodies from ID serum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      DC depletion induces PBC\u2010like serological and histological features, implicating DC dysfunction in immune dysregulation through CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell activation and anti\u2010PDCE\u20102 antibody production. Our ID and IP models show that both T\u2010cell responses and autoantibodies are essential contributors to PBC pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hepr.70014","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T10:27:12Z","timestamp":1754476032000},"page":"1471-1485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dendritic Cell\u2010Depleted Mice Develop the Autoimmune Biliary Disease That Serologically and Pathogenically Models Human Primary Biliary Cholangitis"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7744-5083","authenticated-orcid":false,"given":"Jiaqi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Graduate School of Medicine Chiba University  Chiba City Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Division of Advanced Preventive Medicine Department of Gastroenterology Graduate School of Medicine Chiba University  Chiba City Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingpeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Advanced Genome Medicine The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Advanced Genome Medicine The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ru","sequence":"additional","affiliation":[{"name":"Division of Advanced Genome Medicine The Institute of Medical Science The University of Tokyo  Tokyo 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