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Originally published online as doi:10.1189/JLB.0309135 on June 18, 2009

Published online before print June 18, 2009
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(Journal of Leukocyte Biology. 2009;86:513-528.)
© 2009 Society for Leukocyte Biology

Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases

Bin Gao1, Svetlana Radaeva2 and Ogyi Park

Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA

1. Correspondence: Section on Liver Biology, NIAAA/NIH, 5625 Fishers Lane, Room 2S-33, Bethesda, MD 20892, USA. E-mail: bgao{at}mail.nih.gov

Hepatic lymphocytes are enriched in NK and NKT cells that play important roles in antiviral and antitumor defenses and in the pathogenesis of chronic liver disease. In this review, we discuss the differential distribution of NK and NKT cells in mouse, rat, and human livers, the ultrastructural similarities and differences between liver NK and NKT cells, and the regulation of liver NK and NKT cells in a variety of murine liver injury models. We also summarize recent findings about the role of NK and NKT cells in liver injury, fibrosis, and repair. In general, NK and NKT cells accelerate liver injury by producing proinflammatory cytokines and killing hepatocytes. NK cells inhibit liver fibrosis via killing early-activated and senescent-activated stellate cells and producing IFN-{gamma}. In regulating liver fibrosis, NKT cells appear to be less important than NK cells as a result of hepatic NKT cell tolerance. NK cells inhibit liver regeneration by producing IFN-{gamma} and killing hepatocytes; however, the role of NK cells on the proliferation of liver progenitor cells and the role of NKT cells in liver regeneration have been controversial. The emerging roles of NK/NKT cells in chronic human liver disease will also be discussed. Understanding the role of NK and NKT cells in the pathogenesis of chronic liver disease may help us design better therapies to treat patients with this disease.

Key Words: NK • NKT • liver • poly I:C