{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:40:49Z","timestamp":1747186849805,"version":"3.40.5"},"reference-count":47,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T00:00:00Z","timestamp":1562716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Four major autoimmune diseases target the liver. They develop because of bile duct destruction, leading to chronic cholestasis or result from hepatocyte damage like autoimmune hepatitis (AIH). Interestingly, some patients simultaneously show features of both cholangitis and AIH. Our goal was to mimic such concurrent characteristics in a mouse model that would help deciphering mechanisms possibly involved in an inflammatory crosstalk between cholestatic disease and hepatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>M<jats:italic>dr2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice, which spontaneously develop sclerosing cholangitis because of accumulation of toxic bile salts, were infected with adenovirus (Ad) encoding human Cytochrome P4502D6 (hCYP2D6), the major target autoantigen in type\u20102 AIH, to trigger hepatocyte injury. Wild type FVB mice were controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Resulting Ad\u2010<jats:italic>Mdr2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice presented with cholangitis, fibrosis and cellular infiltrations that were higher than in <jats:italic>Mdr2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> or Ad\u2010FVB mice. Increased levels of anti\u2010neutrophil cytoplasmic antibodies but similar anti\u2010hCYP2D6 antibody titres were detected in Ad\u2010<jats:italic>Mdr2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> compared to <jats:italic>Mdr2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> and Ad\u2010FVB mice respectively. IFN\u03b3\u2010expressing hCYP2D6\u2010specific CD4 T cells declined, whereas hCYP2D6\u2010specific CD8 T cells increased in Ad\u2010<jats:italic>Mdr2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> compared to Ad\u2010FVB mice. The overall T cell balance in Ad\u2010<jats:italic>Mdr2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice was a combination of a type 17\u00a0T cell response typically found in <jats:italic>Mdr2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice with a type 1 dominated T cell response characteristic for Ad\u2010FVB mice. Simultaneously, the type 2\u00a0T cell compartment was markedly reduced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Experimental hepatitis induction in a mouse with sclerosing cholangitis results in a disorder which represents not simply the sum of the individual characteristics but depicts a more complex entity which urges on further analysis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14183","type":"journal-article","created":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T14:58:46Z","timestamp":1561129126000},"page":"2330-2340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of adenovirus\u2010induced hepatocyte damage on chronic bile duct inflammation in a sclerosing cholangitis mouse model"],"prefix":"10.1111","volume":"39","author":[{"given":"Sina","family":"Fuchs","sequence":"first","affiliation":[{"name":"Pharmazentrum Frankfurt \/ ZAFES Goethe University 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