Regulation and functional roles of chemokines in liver diseases

Inflammation is a major contributor to the pathogenesis of almost all liver diseases. Low-molecular-weight proteins called chemokines are the main drivers of liver infiltration by immune cells such as macrophages, neutrophils and others during an inflammatory response. During the past 25 years, tremendous progress has been made in understanding the regulation and functions of chemokines in the liver. This Review summarizes three main aspects of the latest advances in the study of chemokine function in liver diseases. First, we provide an overview of chemokine biology, with a particular focus on the genetic and epigenetic regulation of chemokine transcription as well as on the cell type-specific production of chemokines by liver cells and liver-associated immune cells. Second, we highlight the functional roles of chemokines in liver homeostasis and their involvement in progression to disease in both human and animal models. Third, we discuss the therapeutic opportunities targeting chemokine production and signalling in the treatment of liver diseases, such as alcohol-associated liver disease and nonalcoholic steatohepatitis, including the relevant preclinical studies and ongoing clinical trials.