{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:06:04Z","timestamp":1791234364553,"version":"4.1.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2001,5,1]],"date-time":"2001-05-01T00:00:00Z","timestamp":988675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Autoimmune hepatitis (AIH) in humans arises spontaneously in genetically susceptible individuals and is associated with the presence of Th1 cells in the liver. The understanding of AIH has advanced more slowly than that of other organ-specific autoimmune diseases, however, largely because of the lack of an appropriate animal model. We now describe a new mouse model characterized by spontaneous development of necroinflammatory hepatitis that is restricted by genetic background. Mice deficient in the immunomodulatory cytokine TGF-\u03b21 were extensively back-bred to the BALB\/c background. The BALB\/c background dramatically modified the phenotype of TGF-\u03b21\u2212\/\u2212 mice: specifically, BALB\/c-TGF-\u03b21\u2212\/\u2212 mice developed a lethal necroinflammatory hepatitis that was not observed in TGF-\u03b21\u2212\/\u2212 mice on a different genetic background. BALB\/c background TGF-\u03b21\u2212\/\u2212 livers contained large numbers of activated CD4+ T cells that produced large quantities of IFN-\u03b3, but little IL-4, identifying them as Th1 cells. BALB\/c background TGF-\u03b21\u2212\/\u2212\/IFN-\u03b3\u2212\/\u2212 double knockout mice, generated by cross-breeding, did not develop necroinflammatory hepatitis, demonstrating that IFN-\u03b3 is mechanistically required for its pathogenesis. This represents the first murine model of hepatitis that develops spontaneously, is restricted by genetic background, and is dependent upon the Th1 cytokine IFN-\u03b3, and that thus recapitulates these important aspects of AIH.<\/jats:p>","DOI":"10.4049\/jimmunol.166.10.6413","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:28:25Z","timestamp":1398032905000},"page":"6413-6422","source":"Crossref","is-referenced-by-count":67,"title":["Genetic Regulation of Autoimmune Disease: BALB\/c Background TGF-\u03b21-Deficient Mice Develop Necroinflammatory IFN-\u03b3-Dependent Hepatitis"],"prefix":"10.1093","volume":"166","author":[{"given":"James D","family":"Gorham","sequence":"first","affiliation":[{"name":"Department of Pathology, Dartmouth Medical School , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack T","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dartmouth Medical School , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dartmouth Medical School , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynnie A","family":"Rudner","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dartmouth Medical School , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A","family":"French","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dartmouth Medical School , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,5,15]]},"reference":[{"key":"2026020209191734400_R1","first-page":"35","volume-title":"Autoimmune Liver Diseases","year":"1998"},{"key":"2026020209191734400_R2","first-page":"701","volume-title":"Hepatology","year":"1991"},{"key":"2026020209191734400_R3","first-page":"851","volume-title":"Hepatology","year":"1999"},{"key":"2026020209191734400_R4","first-page":"49","volume-title":"Hepatology","year":"2000"},{"key":"2026020209191734400_R5","first-page":"816","volume-title":"J. 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