Impairment of liver regeneration correlates with activated hepatic NKT cells in HBV transgenic mice
Impairment of liver regeneration correlates with activated hepatic NKT cells in HBV transgenic mice
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HBV 转基因小鼠肝脏再生受损与激活的肝脏 NKT 细胞相关
DOI：
10.1002/hep.21597
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发表时间：
2007-06-01
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：
Dong, Zhongjun;Zhang, Jianhong;Tian, Zhigang
一小部分HBV携带者有患肝癌的风险。由于肝脏具有很强的再生能力，手术切除肝癌或健康肝脏移植是治疗HBV引起的肝癌的替代选择。HBV感染如何影响肝切除或移植肝的再生仍然是一个谜。我们报告，部分肝切除术（PHx）诱导的肝再生减少HBV转基因（HBV-tg）小鼠，人类HBV感染的模型。PHx显著触发了HBV-tg小鼠肝切除肝脏中自然杀伤T（NKT）细胞的积累，同时在肝再生的早期阶段增强了干扰素γ（IFN-γ）的产生和肝NKT细胞上的CD 69表达。HBV-tg小鼠的肝再生障碍在很大程度上通过NKT细胞去除而得到改善，但不能通过自然杀伤（NK）细胞去除。阻断CD 1d-NKT细胞相互作用可显著减轻NKT细胞活化及其对再生肝细胞的抑制作用。IFN-γ的中和作用增强PHx后HBV-tg小鼠中溴脱氧尿苷的掺入，IFN-γ主要诱导肝细胞周期阻滞。从再生的HBV-tg肝连续转移NKT细胞，而不是从正常小鼠，可以抑制受体小鼠的肝再生。结论：活化的NKT细胞负性调节PHx模型中HBV-tg小鼠的肝再生。
A fraction of HBV carriers have a risk to develop liver cancer. Because liver possesses a strong regeneration capability, surgical resection of cancerous liver or transplantation with healthy liver is an alternate choice for HBV-caused hepatocarcinoma therapy. How HBV infection affects the regeneration of hepatectomized or transplanted liver remains elusive. We report that partial hepatectomy (PHx)-induced liver regeneration was reduced in HBV transgenic (HBV-tg) mice, a model of human HBV infection. PHx markedly triggered natural killer T (NKT) cell accumulation in the hepatectomized livers of HBV-tg mice, simultaneously with enhanced interferon gamma (IFN-gamma) production and CD69 expression on hepatic NKT cells at the early stage of liver regeneration. The impairment of liver regeneration in HBV-tg mice was largely ameliorated by NKT cell depletion, but not by natural killer (NK) cell depletion. Blockage of CD1d-NKT cell interaction considerably alleviated NKT cell activation and their inhibitory effect on regenerating hepatocytes. Neutralization of IFN-gamma enhanced bromodeoxyuridine incorporation in HBV-tg mice after PHx, and IFN-gamma mainly induced hepatocyte cell cycle arrest. Adoptive transfer of NKT cells from regenerating HBV-tg liver, but not from normal mice, could inhibit liver regeneration in recipient mice. Conclusion: Activated NKT cells negatively regulate liver regeneration of HBV-tg mice in the PHx model.