title: Increased susceptibility to liver injury in hepatitis B virus transgenic mice involves NKG2D-ligand interaction and natural killer cells.
abstract: The innate immunopathogenesis responsible for the susceptibility to hepatocyte injury in chronic hepatitis B surface antigen carriers is not well defined. In this study, hepatitis B virus (HBV) transgenic mice (named HBs-Tg) were oversensitive to liver injury after immunologic [polyinosinic:polycytidylic acid or concanavalin A (ConA)] or chemical (CCl4) triggering. It was then found that the nonhepatotoxic low dose of ConA for wild-type mice induced severe liver injury in HBs-Tg mice, which was dependent on the accumulated intraheptic natural killer (NK) cells. Expressions of NKG2D ligands (Rae-1 and Mult-1) in hepatocytes were markedly enhanced upon ConA stimulation in HBs-Tg mice, which greatly activated hepatic NK cells via NKG2D/Rae-1 or Mult-1 recognition. Interestingly, the presence of NK T cells was necessary for NK cell activation and worked as positive helper cell possibly by producing interferon-gamma and interleukin-4 in this process.
  
  
  CONCLUSIONS
  Our findings for the first time suggested the critical role of NKG2D recognition of hepatocytes by NK cells in oversensitive liver injury during chronic HBV infection.
authors.affiliation: Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Chen
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Dong
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D002352:Carrier Proteins / Q000378:metabolism; D002353:Carrier State / Q000276:immunology*; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology* / Q000473:pathology; D003208:Concanavalin A / Q000633:toxicity; D004198:Disease Susceptibility; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008099:Liver / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell
chemical_list: D002352:Carrier Proteins; D006514:Hepatitis B Surface Antigens; D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C468260:UL16 binding protein 1, mouse; D003208:Concanavalin A; D002251:Carbon Tetrachloride