Hepatic Immune Microenvironment in Alcoholic and Nonalcoholic Liver Disease

Abstract

Many types of innate (natural killer cells, natural killer T cells, and Kupffer cells/macrophages) and adaptive (T cells and B cells) immune cells are enriched within the liver and function in liver physiology and pathology. Liver pathology is generally induced by two types of immunologic insults: failure to eliminate antigens derived from the gastrointestinal tract which are important for host defense and an impaired tissue protective tolerance mechanism that helps reduce the negative outcomes of immunopathology. Accumulating evidence from the last several decades suggests that hepatic immune cells play an important role in the pathogenesis of alcoholic and nonalcoholic liver injury and inflammation in humans and mice. Here, we focus on the roles of innate and adaptive immune cells in the development and maintenance of alcoholic liver disease and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Additionally, the pathogenesis of liver disease and new therapeutic targets for preventing and treating alcoholic liver disease and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis are discussed.

Figure 1

Diverse types of hepatic immune cells in the development of liver diseases. In the liver, actions and interactions of immune cells with hepatocytes are important for the maintenance of tissue homeostasis as well as the pathogenesis of alcoholic or nonalcoholic liver diseases.

Figure 2

Chronic alcohol consumption impairs the functional properties of both innate and adaptive immune cells in the liver. Chronic alcohol intake results in the activation of innate immunity components, such as KCs/macrophages, and the inhibition of innate immunity components, such as NK and NKT cells, contributing to the pathogenesis of ALD. Moreover, adaptive immunity including T cells and B cells is altered by alcohol consumption, leading to the progression of ALD.

Figure 3

Functional properties of both innate and adaptive immune cells in the development of NAFLD. Diverse types of immune cells are involved in the pathogenesis of NAFLD/NASH. T and B cells, NK and NKT cells, and KCs/macrophages generally promote hepatic inflammation during the development of NAFLD/NASH. However, Treg cells and eosinophils are implicated in the improvement of NAFLD.