Increased susceptibility to liver injury in hepatitis B virus transgenic mice involves NKG2D-ligand interaction and natural killer cells
Increased susceptibility to liver injury in hepatitis B virus transgenic mice involves NKG2D-ligand interaction and natural killer cells
复制标题
乙型肝炎病毒转基因小鼠对肝损伤的易感性增加涉及 NKG2D-配体相互作用和自然杀伤细胞
DOI：
10.1002/hep.21872
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发表时间：
2007-09-01
期刊：
影响因子：
13.5
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
--
作者：
Chen, Yongyan;Wei, Haiming;Tian, Zhigang
慢性乙肝表面抗原携带者对肝细胞损伤的易感性的先天免疫发病机制尚未明确。在本研究中，乙肝病毒转基因小鼠(命名为HBs-TG)在免疫[多肌苷：多胞苷或刀豆蛋白A(ConA)]或化学(CCl4)触发后对肝损伤过度敏感。随后发现，野生型小鼠无肝毒性的小剂量ConA可引起HBs-TG小鼠严重的肝损伤，这种损伤依赖于蓄积的肝内自然杀伤细胞(NK细胞)。ConA刺激HBs-TG小鼠肝细胞NKG2D配体(RAE-1和MULT-1)的表达显著增强，并通过识别NKG2D/RAE-1或MULT-1激活肝NK细胞。有趣的是，NK T细胞的存在是NK细胞激活所必需的，并可能通过在这一过程中产生干扰素-γ和白介素4而发挥阳性辅助细胞的作用。结论：本研究首次提示NK细胞对肝细胞的NKG2D识别在慢性乙肝病毒感染过程中的过敏性肝损伤中起重要作用。
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. 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.