Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.

Abstract

The liver is a central hub in lipid, carbohydrate and protein metabolism and protects against gut-derived antigens and toxins. The etiology of liver diseases includes altered metabolism, viral infections, autoimmunity, toxins and genetic alterations. Liver-resident cells, including hepatocytes, biliary epithelial cells, endothelial cells, and hepatic stellate cells, are essential for liver function and homeostasis but may also drive the development of inflammation, fibrosis, cirrhosis and liver cancer via interactions with immune cells. This review highlights the often-underappreciated contributions of epithelial, endothelial and mesenchymal liver cells in regulating inflammation and immunity across various liver diseases, emphasizing their importance in disease onset, progression and regression. Immune cells and their mediators also play a role in stimulating liver regeneration and repair following injury. Recent findings on the bidirectional interactions between immune cells and resident liver cells provide deeper insights into the underlying pathophysiology and identify novel therapeutic targets for the treatment of liver disease.