Hepatic stellate cells, liver innate immunity, and hepatitis C virus

Chronic hepatitis C virus ( HCV ) infection can cause liver damage, ranging from mild to more severe conditions, such as fibrosis and cirrhosis. Hepatic stellate cell ( HSC ) activation is a key event in HCV ‐induced liver fibrosis. HSC s express several HCV coreceptors that interact with HCV proteins, promoting liver fibrogenesis. In addition, HSC s have the ability to engulf apoptotic bodies of hepatocytes induced by HCV and trigger a profibrogenic response. Recent studies have suggested that HSC s may play a novel role in the liver innate immunity. HSC s enhanced differentiation and accumulation of regulatory T cells. HSC s‐activated natural killer cells could produce γ‐interferon that inhibits HCV replication. Importantly, HSC s possess functional Toll‐like receptor‐3 and retinoic acid‐inducible gene I that can be activated by their ligands (poly I  :  C , 5'ppp‐dsRNA), leading to the induction of interferon and inhibition of HCV replication in hepatocytes. These new observations highlight the importance of HSC s in liver immunity against HCV , which is the focus of this review paper.