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Increased susceptibility to liver injury in hepatitis B virus transgenic mice involves NKG2D‐ligand interaction and natural killer cells
Author(s) -
Chen Yongyan,
Wei Haiming,
Sun Rui,
Dong Zhongjun,
Zhang Jian,
Tian Zhigang
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21872
Subject(s) - nkg2d , liver injury , hepatocyte , immunology , concanavalin a , hepatitis , natural killer cell , interleukin 12 , genetically modified mouse , hepatitis b virus , interferon , biology , virus , chemistry , transgene , cytotoxicity , endocrinology , cytotoxic t cell , biochemistry , in vitro , gene
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 (CCl 4 ) 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‐γ and interleukin‐4 in this process. Conclusion : 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. (H EPATOLOGY 2007.)