Review
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World J Gastroenterol. Oct 7, 2010; 16(37): 4652-4660
Published online Oct 7, 2010. doi: 10.3748/wjg.v16.i37.4652
Roles of liver innate immune cells in nonalcoholic fatty liver disease
Yu-Tao Zhan, Wei An
Yu-Tao Zhan, Department of Gastroenterology and Hepatology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
Wei An, Department of Cell Biology, Capital Medical University, Beijing 100069, China
Author contributions: Zhan YT and An W contributed equally to this paper.
Supported by Beijing Municipal Laboratory for Liver Protection and Regulation of Regeneration, Beijing, China
Correspondence to: Wei An, MD, PhD, Department of Cell Biology, Capital Medical University, Beijing 100069, China. anwei@ccmu.edu.cn
Telephone: +86-10-83911495 Fax: +86-10-83911496
Received: April 6, 2010
Revised: June 3, 2010
Accepted: June 10, 2010
Published online: October 7, 2010
Abstract

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the United States and other developed countries and is expected to increase in the next few years. Emerging data suggest that some patients with NAFLD may progress to nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. NAFLD can also promote the development and progression of disease in other organ systems, such as the cardiovascular and endocrine (i.e. diabetes) systems. Thus, understanding the pathogenesis of NAFLD is of great clinical importance and is critical for the prevention and treatment of the disease. Although the “two-hit hypothesis” is generally accepted, the exact pathogenesis of NAFLD has not been clearly established. The liver is an important innate immune organ with large numbers of innate immune cells, including Kupffer cells (KCs), natural killer T (NKT) cells and natural killer (NK) cells. Recent data show that an imbalance in liver cytokines may be implicated in the development of fatty liver disease. For example, Th1 cytokine excess may be a common pathogenic mechanism for hepatic insulin resistance and NASH. Innate immune cells in the liver play important roles in the excessive production of hepatic Th1 cytokines in NAFLD. In addition, liver innate immune cells participate in the pathogenesis of NAFLD in other ways. For example, activated KCs can generate reactive oxygen species, which induce liver injury. This review will focus primarily on the possible effect and mechanism of KCs, NKT cells and NK cells in the development of NAFLD.

Keywords: Innate immune cells; Nonalcoholic fatty liver disease; Kupffer cell; Natural killer T cell; Natural killer cell