{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:15:49Z","timestamp":1791296149475,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T00:00:00Z","timestamp":1260748800000},"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":[[2010,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The role of liver NK cells in virus-induced severe viral hepatitis and, subsequently, hepatic failure is not well defined. In this study, we investigated the role of liver NK cells in the development of hepatocyte necrosis in fulminant hepatic failure (FHF)and acute-on-chronic liver failure (ACLF) because of viral infection. A mouse model of FHF induced by murine hepatitis virus strain 3 (MHV-3) was used to study the role of liver NK cells. Samples from patients with hepatitis B virus-related ACLF (HBV-ACLF) were examined. After MHV-3 infection, the number of NK cells in livers of BALB\/cJ mice increased markedly, peaked at 48 h postinfection, and remained at a high level until sacrifice. In peripheral blood, spleen, and bone marrow, this number decreased significantly. Expression of CD69, cytotoxic activity, and intracellular IFN-\u03b3 and TNF-\u03b1 production by liver NK cells at 48 h postinfection were all significantly upregulated. Depletion of NK cells 24 h post-MHV-3 infection increased the mice survival from 0 of 18 (0%) to 4 of 18 (22.2%). Highly activated liver NK cells were cytotoxic to MHV-3-infected hepatocytes and this effect was markedly inhibited by anti-Fas ligand (FasL) plus anti-NKG2D mAbs. Furthermore, the accumulation of hepatic NK cells and increased expression of FasL and natural cytotoxicity receptors (NKp30 and NKp46) on the peripheral NK cells from patients with HBV-ACLF were correlated with disease progression. These results indicate NK cells play a pivotal role in the pathogenesis of FHF and HBV-ACLF, in which process Fas\/FasL and NKG2D\/NKG2D ligand pathway contribute to the liver NK cell-mediated hepatocyte injury.<\/jats:p>","DOI":"10.4049\/jimmunol.0900687","type":"journal-article","created":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T03:38:26Z","timestamp":1259638706000},"page":"466-475","source":"Crossref","is-referenced-by-count":121,"title":["Increased Killing of Liver NK Cells by Fas\/Fas Ligand and NKG2D\/NKG2D Ligand Contributes to Hepatocyte Necrosis in Virus-Induced Liver Failure"],"prefix":"10.1093","volume":"184","author":[{"given":"Yong","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Infectious Disease, Institute of Infectious Disease , Wuhan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Institute of Infectious Disease , Wuhan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meifang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Institute of Infectious Disease , Wuhan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Institute of Infectious Disease , Wuhan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Institute of Infectious Disease , Wuhan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Institute of Infectious Disease , Wuhan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeguang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Institute of Infectious Disease , Wuhan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Institute of Infectious Disease , Wuhan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanlong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Affiliated Provincial Hospital, Anhui Medical University , Hefei,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology , Wuhan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Institute of Infectious Disease , Wuhan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,14]]},"reference":[{"key":"2025032603361497400_r1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1172\/JCI18114","article-title":"The Fgl2\/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis.","volume":"112","author":"Marsden","year":"2003","journal-title":"J. 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