{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T22:19:12Z","timestamp":1784067552279,"version":"3.55.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":189,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB738 B4"],"award-info":[{"award-number":["SFB738 B4"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KFO250 Project 7"],"award-info":[{"award-number":["KFO250 Project 7"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union Euraps (LSHM-CT-2005)","award":["005223 (FP6\/EU)"],"award-info":[{"award-number":["005223 (FP6\/EU)"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:p>Autoimmune polyendocrine syndrome type 1 (APS\u20101) is caused by mutations of the autoimmune regulator (<jats:italic toggle=\"yes\">AIRE)<\/jats:italic> gene. Mouse studies have shown that this results in defective negative selection of T cells and defective early seeding of peripheral organs with regulatory T cells (Tregs). Aire deficiency in humans and mice manifests as spontaneous autoimmunity against multiple organs, and 20% of patients develop an autoimmune hepatitis (AIH). To study AIH in APS\u20101, we generated a murine model of human AIH on a BALB\/c mouse background, in which <jats:italic toggle=\"yes\">Aire<\/jats:italic> is truncated at exon 2. A subgroup of 24% of mice is affected by AIH, characterized by lymphoplasmacytic and periportal hepatic infiltrates, autoantibodies, elevated aminotransferases, and a chronic and progressive course of disease. Disease manifestation was dependent on specific <jats:italic toggle=\"yes\">Aire<\/jats:italic> mutations and the genetic background of the mice. Though intrahepatic Treg numbers were increased and hyperproliferative, the intrahepatic CD4\/CD8 ratio was decreased. The targets of the adaptive autoimmune response were polyspecific and not focussed on essential autoantigens, as described for other APS\u20101\u2010related autoimmune diseases. The AIH could be treated with prednisolone or adoptive transfer of polyspecific Tregs. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Development of AIH in APS\u20101 is dependent on specific <jats:italic toggle=\"yes\">Aire<\/jats:italic> mutations and genetic background genes. Autoimmune response is polyspecific and can be controlled by steroids or transfer with Tregs. This might enable new treatment options for patients with AIH. (H<jats:sc>epatology<\/jats:sc> 2015;61:1295\u20131305)<\/jats:p>","DOI":"10.1002\/hep.27639","type":"journal-article","created":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T00:17:09Z","timestamp":1418084229000},"page":"1295-1305","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":39,"title":["Autoimmune hepatitis in a murine autoimmune polyendocrine syndrome type 1 model is directed against multiple autoantigens"],"prefix":"10.1097","volume":"61","author":[{"given":"Matthias","family":"Hardtke\u2010Wolenski","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology,Hannover Medical School,Hannover,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Taubert","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology,Hannover Medical 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