The liver is a critical hub of metabolism responsible for metabolizing a myriad of substances including glucose, lipid, xenobiotics, and alcohol. Over the years, we have come to know that the liver is not only the site of metabolism but also a central immunological organ. Apart from Kupffer cells, the liver-resident macrophages, various innate and adaptive immune cells such as natural killer and natural killer T cells, are also enriched in the liver. The presence of these immune cells do not confine the hepatic immune response to invading pathogens derived from the gastrointestinal tracts, but also damage-associated pattern molecules (DAMPs) released from damaged hepatocytes.

Mild liver diseases arise from metabolic disorders such as type 2 diabetes, obesity, or alcohol disorder. Homeostatic imbalance such as increasing fat accumulation or reactive oxygen species production contributes to hepatic injury. Inflammatory cytokines and metabolic byproducts released from hepatocytes stimulate excessive immune response, which in turn promotes disease progression from simple steatosis to severe hepatitis. Taken together, the interaction between immunologic and metabolic pathways is a key to understanding the pathogenesis of liver disease.

Our laboratory conducts translational studies on alcoholic and nonalcoholic fatty liver, steatohepatitis, and end-stage liver diseases such as liver fibrosis and hepatocellular carcinoma based on various animal models. An integrative perspective of the immuno-metabolic axis can provide novel therapeutic targets and treatment of liver disease.