Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Viral Immunol. 2022 Nov;35(9):597-608. doi: 10.1089/vim.2022.0029. Epub 2022 Sep 13.
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.
多项研究表明乙型肝炎病毒（HBV）感染是由巨噬细胞介导的，而（B7-H4，VTCN-1）蛋白在 HBV 相关肝细胞癌（HBV-HCC）的免疫调节中发挥重要作用。然而，HBV、巨噬细胞和之间的关系尚未得到研究。在这项研究中，使用 HBV 感染的小鼠模型和 HBV 细胞系与巨噬细胞的共培养来观察巨噬细胞的变化以及 HBV 感染后表达的变化。通过逆转录定量聚合酶链反应、酶联免疫吸附试验、western blot 和流式细胞术分析了 HBV 标志物（HBeAg、HBsAg）、免疫负调节剂（B7x）、辅助性 T 细胞 17（Th17）/调节性 T 细胞（Treg）相关细胞因子以及巨噬细胞标志物的表达以及巨噬细胞凋亡和细胞周期的变化。HBV 感染后，和中 HBsAg、HBeAg 和 B7x 的表达增加，巨噬细胞表面标志物和 Treg 细胞分泌相关细胞因子（IL-10 和 TGF-）的水平发生改变。巨噬细胞凋亡增加，细胞周期停滞。除了细胞周期外，当下调时，这些作用都被逆转。因此，HBV 感染可以促进 B7x 的表达，进而调节 Th17/Treg 平衡，并影响 HBsAg 和 HBeAg 的表达。表达可能涉及促进巨噬细胞极化和凋亡。这些结果表明是 HBV 免疫治疗的一个新靶点。
