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Here, NK cells up-regulated a coinhibitory receptor, T-cell Ig and ITIM domain (TIGIT), during challenge with the viral double-stranded RNA (dsRNA) analog poly I:C. Blocking TIGIT by antibody treatment<\/jats:bold>\n                                 <jats:bold>\n                                    in vivo\n                                 <\/jats:bold>\n                                 <jats:bold>or a genetic deficiency in<\/jats:bold>\n                                 <jats:bold>\n                                    Tigit\n                                 <\/jats:bold>\n                                 <jats:bold>enhanced NK cell activation and aggravated liver injury in a poly I:C\/D-GalN-induced model of acute fulminant hepatitis, suggesting that TIGIT is normally required for protecting against NK cell-mediated liver injury. Furthermore, adoptively transferring<\/jats:bold>\n                                 <jats:bold>\n                                    Tigit\u2212\/\u2212\n                                    \n                                 <\/jats:bold>\n                                 <jats:bold>NK cells into NK cell-deficient<\/jats:bold>\n                                 <jats:bold>\n                                    Nfil3\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mice also resulted in elevated liver injury. Reconstituting Kupffer cell-depleted mice with poliovirus receptor (PVR\/CD155, a TIGIT ligand)-silenced Kupffer cells led to aggravated liver injury in a TIGIT-dependent manner. Blocking TIGIT in an NK-Kupffer cell coculture<\/jats:bold>\n                                 <jats:bold>\n                                    in vitro\n                                 <\/jats:bold>\n                                 <jats:bold>enhanced NK cell activation and interferon-gamma (IFN-\u03b3) production in a PVR-dependent manner. We also found that TIGIT was up-regulated selectively on NK cells and protected against liver injury in an acute adenovirus infection model in both an NK cell- and Kupffer cell-dependent manner. Knocking down PVR in Kupffer cells resulted in aggravated liver injury in response to adenovirus infection in a TIGIT-dependent manner.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion :<\/jats:title>\n            <jats:p>\n                                 <jats:bold>TIGIT negatively regulates NK-Kupffer cell crosstalk and alleviates liver injury in response to poly I:C\/D-GalN challenge or acute adenovirus infection, suggesting a novel mechanism of NK cell self-tolerance in liver homeostasis during acute viral infection. (Hepatology 2014;59:1715\u20131725)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.26968","type":"journal-article","created":{"date-parts":[[2013,12,9]],"date-time":"2013-12-09T09:02:37Z","timestamp":1386579757000},"page":"1715-1725","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":56,"title":["T-Cell Ig and ITIM Domain Regulates Natural Killer Cell Activation in Murine Acute Viral Hepatitis"],"prefix":"10.1097","volume":"59","author":[{"given":"Jiacheng","family":"Bi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-14-20250207","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ni1581","article-title":"Up on the tightrope: natural killer cell activation and inhibition.","volume":"9","author":"Lanier","year":"2008","journal-title":"Nat Immunol"},{"key":"R2-14-20250207","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nature10624","article-title":"Natural killer cells act as rheostats modulating antiviral T cells.","volume":"481","author":"Waggoner","year":"2012","journal-title":"Nature"},{"key":"R3-14-20250207","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1126\/science.1215621","article-title":"Tuning of natural killer cell reactivity by NKp46 and Helios calibrates T cell responses.","volume":"335","author":"NarniMancinelli","year":"2012","journal-title":"Science"},{"key":"R4-14-20250207","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1136\/jclinpath-2012-201097","article-title":"Participation of natural killer cells in the pathogenesis of bile duct lesions in biliary atresia.","volume":"66","author":"Okamura","year":"2013","journal-title":"J Clin Pathol"},{"key":"R5-14-20250207","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.23977","article-title":"Hypercytolytic activity of hepatic natural killer cells correlates with liver injury in chronic hepatitis B patients.","volume":"53","author":"Zhang","year":"2011","journal-title":"Hepatology"},{"key":"R6-14-20250207","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/hep.21993","article-title":"Therapeutic RNA silencing of CysX3Cys chemokine ligand 1 gene prevents mice from adenovirus vectorinduced acute liver injury.","volume":"47","author":"Chen","year":"2008","journal-title":"Hepatology"},{"key":"R7-14-20250207","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.immuni.2004.06.007","article-title":"TLR9dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function.","volume":"21","author":"Krug","year":"2004","journal-title":"Immunity"},{"key":"R8-14-20250207","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.immuni.2007.03.006","article-title":"Dendritic cells prime natural killer cells by transpresenting interleukin 15.","volume":"26","author":"Lucas","year":"2007","journal-title":"Immunity"},{"key":"R9-14-20250207","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1084\/jem.20091181","article-title":"Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)mediated activation of mouse NK cells.","volume":"206","author":"McCartney","year":"2009","journal-title":"J Exp Med"},{"key":"R10-14-20250207","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/ni1197","article-title":"Transforming growth factorbeta controls T helper type 1 cell development through regulation of natural killer cell interferongamma.","volume":"6","author":"Laouar","year":"2005","journal-title":"Nat Immunol"},{"key":"R11-14-20250207","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-immunol-020711-075005","article-title":"Controlling natural killer cell responses: integration of signals for activation and inhibition.","volume":"31","author":"Long","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"R12-14-20250207","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.4049\/jimmunol.172.4.2001","article-title":"Lanier LL. 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