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Several studies in human and mouse suggested a protective role for IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a in liver inflammation, and we previously demonstrated that hepatocytes produce high levels of IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a in response to inflammatory challenge in vitro and in vivo. In the present study, we investigated the production and the biological function of hepatocyte\u2010derived IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a in concanavalin A<\/jats:styled-content> (C<\/jats:styled-content>onA<\/jats:styled-content>)\u2010induced hepatitis in mice. We show that the injured liver produces large amounts of IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a and that secreted and intracellular IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a isoforms are produced with different kinetics during the course of hepatitis. By using hepatocyte\u2010specific IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a\u2010deficient mice (IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a\u0394H<\/jats:sup>), we demonstrate that hepatocytes represent the major cellular source of local IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a. Most interestingly, hepatic necrosis and inflammation were increased in IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a\u0394H<\/jats:sup> as compared with wild\u2010type mice during the late phase of the disease, leading to a delayed resolution of hepatitis in IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a\u0394H<\/jats:sup> mice. In conclusion, our results show that the local production of IL<\/jats:styled-content>\u20101R<\/jats:styled-content>a by hepatocytes contributes to the resolution of hepatitis.<\/jats:p>","DOI":"10.1002\/eji.201142204","type":"journal-article","created":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T18:49:03Z","timestamp":1335466143000},"page":"1294-1303","source":"Crossref","is-referenced-by-count":14,"title":["Mice deficient in hepatocyte\u2010specific IL<\/scp>\u20101Ra show delayed resolution of concanavalin A<\/scp>\u2010induced hepatitis"],"prefix":"10.1002","volume":"42","author":[{"given":"C\u00e9line","family":"Lamacchia","sequence":"first","affiliation":[{"name":"Division of Rheumatology University Hospital and Department of Pathology and Immunology University of Geneva School of Medicine Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliana","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University Hospital and Department of Pathology and Immunology University of Geneva School of Medicine Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaby","family":"Palmer","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University Hospital and Department of Pathology and Immunology University of Geneva School of Medicine Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Vesin","sequence":"additional","affiliation":[{"name":"Department of Cellular Physiology and Metabolism University of Geneva School of Medicine Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A.","family":"Seemayer","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG. 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