Immune cells in alcohol-related liver disease.

Alcohol-related liver disease (ALD), which is caused by excessive alcohol consumption, is one of the most common types of liver disease and a primary cause of hepatic injury, with a disease spectrum that includes steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Various lines of evidence have indicated that immune cells play a significant role in the inflammatory processes of ALD. On the one hand, the liver contains various resident immune cells that have been proven to perform different functions in ALD. For example, in the progression of the disease, Kupffer cells (KCs) are activated by lipopolysaccharide-Toll-like receptor 4 signaling and release various proinflammatory cytokines. Moreover, alcohol intake has been shown to depress the function of natural killer cells. Additionally, two types of unconventional T cells (natural killer T cells and mucosal-associated invariant T cells) are involved in the development of ALD. On the other hand, alcohol and many different cytokines stimulate the recruitment and infiltration of circulating immune cells (neutrophils, T cells, macrophages, and mast cells) into the liver. The neutrophils can produce proinflammatory mediators and cause the dysfunction of anti-infection processes. Additionally, alcohol intake can change the phenotype of T cells, resulting in their increased production of interleukin-17. Aside from KCs, infiltrating macrophages have also been observed in patients with ALD, but the roles of all of these cells in the progression of the disease have shown both similarities and differences. Additionally, the activated mast cells are also associated with the development of ALD. Herein, we review the diverse roles of the various immune cells in the progression of ALD.