Long-Yan Chen1, Xiao-Peng Fan1, Yu-Chen Fan1, Jing Zhao1, Shuai Gao1, Feng Li1, Zhao-Xia Qi1, Kai Wang2,3. 1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China. 2. Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China. wangdoc876@126.com. 3. Institute of Hepatology, Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China. wangdoc876@126.com.
Abstract
BACKGROUND: B cell-activating transcription factor (BATF) contributes to Th17 cell differentiation and pathological inflammatory responses. AIMS: This study explored BATF as a regulator of Th17 differentiation in normal and hepatitis B virus (HBV) transgenic mice. METHODS: Normal mice were divided into control, short hairpin RNA (shRNA) scramble, and shRNA BATF groups. HBV transgenic mice were divided into control, entecavir, shRNA scramble, entecavir + vector control, entecavir + shRNA scramble, shRNA BATF, and entecavir + shRNA BATF groups. Serum concentrations of AST, ALT, HBV-DNA, BATF, IL-17, and IL-22 and Th17 cell frequencies in the liver were compared among the groups. Correlations of serum HBV surface antigen (HBsAg), e-antigen (HBeAg), and core antigen (HBcAg) concentrations with BATF mRNA expression and the proportion of Th17 cells in the livers of HBV transgenic mice were also analyzed. RESULTS: Serum AST, ALT, BATF, IL-17, and IL-22 concentrations and Th17 cell proportions were higher in HBV transgenic mice relative to normal controls. Positive correlations of the HBcAg concentration with BATF mRNA and the proportion of Th17 cells were observed in HBV transgenic mice. BATF interference reduced the proportion of Th17 cells and serum IL-17 and IL-22 concentrations and led to obvious downregulation of AST, ALT, BATF, IL-17, and IL-22 expression and a reduced proportion of Th17 cells when combined with entecavir. CONCLUSION: HBV markedly upregulated BATF expression and promoted Th17 cell activation. By contrast, BATF interference significantly impeded the proliferation of Th17 cells and secretion of IL-17 and IL-22 while alleviating hepatic lesions.
BACKGROUND:B cell-activating transcription factor (BATF) contributes to Th17 cell differentiation and pathological inflammatory responses. AIMS: This study explored BATF as a regulator of Th17 differentiation in normal and hepatitis B virus (HBV) transgenic mice. METHODS: Normal mice were divided into control, short hairpin RNA (shRNA) scramble, and shRNA BATF groups. HBVtransgenic mice were divided into control, entecavir, shRNA scramble, entecavir + vector control, entecavir + shRNA scramble, shRNA BATF, and entecavir + shRNA BATF groups. Serum concentrations of AST, ALT, HBV-DNA, BATF, IL-17, and IL-22 and Th17 cell frequencies in the liver were compared among the groups. Correlations of serum HBV surface antigen (HBsAg), e-antigen (HBeAg), and core antigen (HBcAg) concentrations with BATF mRNA expression and the proportion of Th17 cells in the livers of HBVtransgenic mice were also analyzed. RESULTS: Serum AST, ALT, BATF, IL-17, and IL-22 concentrations and Th17 cell proportions were higher in HBVtransgenic mice relative to normal controls. Positive correlations of the HBcAg concentration with BATF mRNA and the proportion of Th17 cells were observed in HBVtransgenic mice. BATF interference reduced the proportion of Th17 cells and serum IL-17 and IL-22 concentrations and led to obvious downregulation of AST, ALT, BATF, IL-17, and IL-22 expression and a reduced proportion of Th17 cells when combined with entecavir. CONCLUSION:HBV markedly upregulated BATF expression and promoted Th17 cell activation. By contrast, BATF interference significantly impeded the proliferation of Th17 cells and secretion of IL-17 and IL-22 while alleviating hepatic lesions.