Immune–metabolic interactions in homeostasis and the progression to NASH

The incidence of non-alcoholic fatty liver disease (NAFLD) has increased significantly over the past two decades. NAFLD ranges from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) and predisposes to fibrosis and hepatocellular carcinoma (HCC). The importance of the immune system in hepatic physiology and in the progression of NAFLD is increasingly recognized. At homeostasis, the liver participates in immune defense against pathogens and in tolerance of gut-derived microbial compounds. Hepatic immune cells also respond to metabolic stimuli and have a role in NAFLD progression to NASH. In this review, we discuss how metabolic perturbations affect immune cell phenotype and function in NAFL and NASH, and then focus on the role of immune cells in liver homeostasis and in the development of NASH.