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The precise role of NK cells in the progression of NASH has yet to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using methionine\u2010 and choline\u2010deficient diets (MCD)\u2010induced NASH model, the role of NK cells was identified in WT mice compared with conventional NK cell\u2013deficient Nfil3<jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After 8\u00a0weeks of MCD treatment, NASH was induced as shown by the significant macrovesicular steatosis, necro\u2010inflammation and fibrosis in the liver of WT B6 mice. In MCD\u2010treated WT B6 mice, the number of NK cells was markedly increased in the liver, but decreased in the spleen. Intrahepatic NK cells exhibited high levels of activation, as evidenced by the expression of CD107a and cytokine production of IFN\u2010\u03b3, TGF\u2010\u03b2 and IL\u201010. Lower expression levels of Ki67 indicated a reduction in the proliferation of intrahepatic NK cells after MCD treatment. Increased expression of CXCL10 in the liver early after MCD treatment led to the increased recruitment of CXCR3<jats:sup>+<\/jats:sup> NK cells into the liver. The MCD\u2010treated Nfil3<jats:sup>\u2212\/\u2212<\/jats:sup> mice showed similar levels of TG and macrovesicular steatosis, thus more inflammatory infiltration and increased collagen deposition in the liver. Furthermore, the depletion of NK cells during MCD\u2010induced NASH caused a significant increase in the infiltration of monocyte\u2010derived macrophages (MoMFs) particularly Ly6C<jats:sup>lo<\/jats:sup> subsets towards M2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Intrahepatic NK cells, recruited through CXCL10\u2010CXCR3 interaction, play a protective role against the fibrosis progression in NASH, which provide us with a better understanding of the immunopathogenesis of NASH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14307","type":"journal-article","created":{"date-parts":[[2019,11,23]],"date-time":"2019-11-23T06:05:55Z","timestamp":1574489155000},"page":"598-608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Hepatic NK cells attenuate fibrosis progression of non\u2010alcoholic steatohepatitis in dependent of CXCL10\u2010mediated recruitment"],"prefix":"10.1111","volume":"40","author":[{"given":"Yuting","family":"Fan","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine Hefei National Laboratory for Physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic Disease School of Life Sciences University of Science and Technology of China Hefei China"},{"name":"Institute of Immunology University of Science and Technology of China Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine Hefei National Laboratory for Physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic Disease School of Life Sciences University of Science and Technology of China Hefei China"},{"name":"Institute of Immunology University of Science and Technology of China Hefei 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