{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:27:04Z","timestamp":1792106824854,"version":"4.4.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4140,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The central role of T cell activation in hepatocellular injury has been well documented. In this article, we provide evidence suggesting that T cells may also play a protective role in liver disease by releasing interleukin-22 (IL-22), a recently identified T cell-derived cytokine whose biological significance is unclear. IL-22 messenger RNA and protein expression are significantly elevated in T cell-mediated hepatitis induced by concanavalin A (ConA) but are less extensively elevated in the carbon tetrachloride-induced liver injury model. Activated CD3<jats:sup>+<\/jats:sup> T cells are likely responsible for the production of IL-22 in the liver after injection of ConA. The IL-22 receptor is normally expressed at high levels by hepatocytes and further induced after ConA injection. IL-22 blockade with a neutralizing antibody reduces signal transducer and activator of transcription factor 3 (STAT3) activation and worsens liver injury in T cell-mediated hepatitis, whereas injection of recombinant IL-22 attenuates such injury. <jats:italic toggle=\"yes\">In vitro<\/jats:italic> treatment with recombinant IL-22 or overexpression of IL-22 promotes cell growth and survival in human hepatocellular carcinoma HepG2 cells. Stable overexpression of IL-22 in HepG2 cells constitutively activates STAT3 and induces expression of a variety of antiapoptotic (<jats:italic toggle=\"yes\">e.g.<\/jats:italic>, Bcl-2, Bcl-xL, Mcl-1) and mitogenic (<jats:italic toggle=\"yes\">e.g.<\/jats:italic>, c-myc, cyclin D1, Rb2, CDK4) proteins. Blocking STAT3 activation abolishes the antiapoptotic and mitogenic actions of IL-22 in hepatic cells. In conclusion, the T cell-derived cytokine IL-22 is a survival factor for hepatocytes; this suggests that T cell activation may also prevent and repair liver injury by releasing hepatoprotective cytokine IL-22 in addition to its previously documented central role in hepatocellular injury. (Hepatology 2004;39:1332-1342.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.20184","type":"journal-article","created":{"date-parts":[[2004,4,26]],"date-time":"2004-04-26T23:02:05Z","timestamp":1083020525000},"page":"1332-1342","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":525,"title":["Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation"],"prefix":"10.1097","volume":"39","author":[{"given":"Svetlana","family":"Radaeva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-na","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20-20241201","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/hep.510300312","article-title":"Pathogenesis of chronic hepatitis C: immunological features of hepatic injury and viral persistence.","volume":"30","author":"Cerny","year":"1999","journal-title":"HEPATOLOGY"},{"key":"R2-20-20241201","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1053\/jhep.2002.30293","article-title":"Frequencies of HCV-specific effector CD4 T cells by flow cytometry: correlation with clinical disease stages.","volume":"35","author":"Rosen","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R3-20-20241201","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1053\/jhep.2001.21162","article-title":"Differential CD4() and CD8() T-cell responsiveness in hepatitis C virus infection.","volume":"33","author":"Chang","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R4-20-20241201","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1053\/gast.2001.22441","article-title":"The lymphoid liver: considerations on pathways to autoimmune injury.","volume":"120","author":"Kita","year":"2001","journal-title":"Gastroenterology"},{"key":"R5-20-20241201","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1053\/jhep.2002.30991","article-title":"Current and novel immunosuppressive therapy for autoimmune hepatitis.","volume":"35","author":"Heneghan","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R6-20-20241201","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/0016-5085(93)90034-A","article-title":"Cell-mediated hepatic injury in alcoholic liver disease. 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