Alcohol-Induced Dendritic Cells and Their Exosomes Promote T-Cell Immunity in Hepatitis B Virus Transgenic Mice and Patients With Chronic Hepatitis B

Abstract

Dendritic cells and the exosomes they secrete play a crucial role in the immune system, and studies have shown that dendritic cell function is dramatically reduced in patients with chronic hepatitis B. Alcohol could stimulate dendritic cell maturation. Consequently, the present work explored the therapeutic effect of alcohol-induced dendritic cells and their exosomes in hepatitis B virus (HBV) infection. We systematically investigated the functional effects of alcohol stimulation and HBV infection on dendritic cells and their exosomes, as well as cocultured alcohol-induced dendritic cells and exosomes with lymphocytes from HBV transgenic mice and chronic hepatitis B patients to study the T cell immune response. Our findings revealed that alcohol significantly accelerated the maturation of bone marrow-derived dendritic cells in mice and dendritic cells in patients with chronic hepatitis B, but had no effect on the DC2.4 cell line. Simultaneously, HBV infection was demonstrated to inhibit dendritic cell activation and maturation, as well as exosomes. More importantly, alcohol-induced dendritic cells enhanced T-cell immunity in HBV transgenic mice and chronic hepatitis B patients, and their exosomes had the same impact. The maturation of dendritic cells and their exosomes can be effectively induced by alcohol. Meanwhile, alcohol-induced maturation of dendritic cells and exosomes can significantly repair the poor T-cell immunity caused by HBV infection, making it a promising novel treatment for chronic hepatitis B patients in the future.