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Impairment of liver regeneration correlates with activated hepatic NKT cells in HBV transgenic mice
Author(s) -
Dong Zhongjun,
Zhang Jianhong,
Sun Rui,
Wei Haiming,
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.21597
Subject(s) - liver regeneration , natural killer t cell , regeneration (biology) , hepatology , hepatocyte , biology , immunology , cancer research , genetically modified mouse , transgene , medicine , t cell , microbiology and biotechnology , immune system , biochemistry , in vitro , gene
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‐γ) 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‐γ enhanced bromodeoxyuridine incorporation in HBV‐tg mice after PHx, and IFN‐γ 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. (H EPATOLOGY 2007.)