{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:15:58Z","timestamp":1791296158336,"version":"4.1.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2016,1,21]],"date-time":"2016-01-21T00:00:00Z","timestamp":1453334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2016,1,21]],"date-time":"2016-01-21T00:00:00Z","timestamp":1453334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>Nonalcoholic steatohepatitis (NASH) affects 3%\u20105% of the U.S. population, having severe clinical complications to the development of fibrosis and end\u2010stage liver diseases, such as cirrhosis and hepatocellular carcinoma. A critical cause of NASH is chronic systemic inflammation promoted by innate immune cells, such as liver macrophages (M\u03d5) and natural killer (NK) cells. However, little is known about how the crosstalk between M\u03d5 and NK cells contributes to regulate NASH progression to fibrosis. In this report, we demonstrate that NKp46<jats:sup>+<\/jats:sup> cells play an important role in preventing NASH progression to fibrosis by regulating M1\/M2 polarization of liver M\u03d5. Using a murine model of NASH, we demonstrate that DX5<jats:sup>+<\/jats:sup>NKp46<jats:sup>+<\/jats:sup> NK cells are increased during disease and play a role in polarizing M\u03d5 toward M1\u2010like phenotypes. This NK's immunoregulatory function depends on the production of interferon\u2010gamma (IFN\u2010\u03b3), but not by granzyme\u2010mediated cytolytic activity. Notably, depletion of NKp46<jats:sup>+<\/jats:sup> cells promotes the development of fibrosis with increased expression of profibrogenic genes as well as skewed M2 M\u03d5 phenotypes in hepatic tissues. <jats:italic toggle=\"yes\">Conclusions:<\/jats:italic> NK cell\u2010derived IFN\u2010\u03b3 may be essential for maintaining a balanced inflammatory environment that promotes tissue integrity and limiting NASH progression to fibrosis. (H<jats:sc>epatology<\/jats:sc> 2016;63:799\u2013812)<\/jats:p>","DOI":"10.1002\/hep.28389","type":"journal-article","created":{"date-parts":[[2015,12,11]],"date-time":"2015-12-11T00:45:36Z","timestamp":1449794736000},"page":"799-812","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":135,"title":["NKp46+ natural killer cells attenuate metabolism\u2010induced hepatic fibrosis by regulating macrophage activation in mice"],"prefix":"10.1097","volume":"63","author":[{"given":"Annie\u2010Carole","family":"Tosello\u2010Trampont","sequence":"first","affiliation":[{"name":"Beirne Carter Center for Immunology Research,University of Virginia,Charlottesville,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Krueger","sequence":"additional","affiliation":[{"name":"Beirne Carter Center for Immunology Research,University of Virginia,Charlottesville,VA"},{"name":"Department of Microbiology, Immunology and Cancer Biology, Beirne Carter Center for Immunology Research,University of Virginia,Charlottesville,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sowmya","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Beirne Carter Center for Immunology Research,University of Virginia,Charlottesville,VA"},{"name":"Department of Microbiology, Immunology and Cancer Biology, Beirne Carter Center for Immunology Research,University of Virginia,Charlottesville,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan G.","family":"Landes","sequence":"additional","affiliation":[{"name":"Beirne Carter Center for Immunology Research,University of Virginia,Charlottesville,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Leitinger","sequence":"additional","affiliation":[{"name":"Department of Pharmacology,University of Virginia,Charlottesville,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young S.","family":"Hahn","sequence":"additional","affiliation":[{"name":"Beirne Carter Center for Immunology Research,University of Virginia,Charlottesville,VA"},{"name":"Department of Microbiology, Immunology and Cancer Biology, Beirne Carter Center for Immunology Research,University of Virginia,Charlottesville,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,1,21]]},"reference":[{"key":"hep28389-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nrgastro.2013.149","article-title":"From NAFLD to NASH to cirrhosis\u2010new insights into disease mechanisms","volume":"10","year":"2013","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"hep28389-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1002\/hep.26091","article-title":"The strange and critical intersection of hepatitis C and lipoprotein metabolism: \u201cC\u2010zing\u201d the 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