Hepatitis B Virus Infection Promotes M2 Polarization of Macrophages by Upregulating the Expression of and .

Several studies have reported that hepatitis B virus (HBV) infection is mediated by macrophages and that the (B7-H4, VTCN-1) protein plays an important role in immune regulation in HBV-associated hepatocellular carcinoma (HBV-HCC). However, the relationship among HBV, macrophages, and has not been studied. In this study, HBV-infected mouse model and coculture of HBV cell lines and macrophages were used to observe the changes in macrophages and the role of after HBV infection. The expression of HBV markers (HBeAg, HBsAg), negative regulator of immunity (B7x), T-helper 17 (Th17)/T-regulatory (Treg)-related cytokines, and macrophage markers, as well as changes in the apoptosis and cell cycle of macrophages were analyzed through reverse transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, western blot, and flow cytometry. The expression of HBsAg, HBeAg, and B7x increased and the levels of macrophage surface marker and Treg cells secrete related cytokines (IL-10 and TGF-) were altered after HBV infection both and . poptosis of macrophages increased, and cell cycle arrest occurred . These effects, except those in the cell cycle, were reversed when was knocked down. Thus, HBV infection can promote the expression of B7x, which in turn regulates the Th17/Treg balance and affects the expression of HBsAg and HBeAg. The mechanism used by likely involves the promotion of macrophage polarization and apoptosis. These results suggest that is a novel target for HBV immunotherapy.