Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China.
Institute of Hepatology, Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China.
Dig Dis Sci. 2019 Mar;64(3):773-780. doi: 10.1007/s10620-018-5392-x. Epub 2018 Nov 29.
B cell-activating transcription factor (BATF) contributes to Th17 cell differentiation and pathological inflammatory responses.
This study explored BATF as a regulator of Th17 differentiation in normal and hepatitis B virus (HBV) transgenic mice.
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.
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.
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.
B 细胞激活转录因子（BATF）有助于 Th17 细胞分化和病理性炎症反应。
本研究旨在探讨 BATF 作为正常和乙型肝炎病毒（HBV）转基因小鼠 Th17 分化的调节因子。
将正常小鼠分为对照组、短发夹 RNA（shRNA）乱序组和 shRNA BATF 组。将 HBV 转基因小鼠分为对照组、恩替卡韦组、shRNA 乱序组、恩替卡韦+载体对照组、恩替卡韦+shRNA 乱序组、shRNA BATF 组和恩替卡韦+shRNA BATF 组。比较各组血清 AST、ALT、HBV-DNA、BATF、IL-17 和 IL-22 浓度及肝内 Th17 细胞频率。分析 HBV 转基因小鼠血清 HBV 表面抗原（HBsAg）、e 抗原（HBeAg）和核心抗原（HBcAg）浓度与 BATF mRNA 表达及肝内 Th17 细胞比例的相关性。
HBV 转基因小鼠血清 AST、ALT、BATF、IL-17 和 IL-22 浓度及 Th17 细胞比例均高于正常对照组。HBV 转基因小鼠 HBcAg 浓度与 BATF mRNA 及 Th17 细胞比例呈正相关。BATF 干扰降低 Th17 细胞比例及血清 IL-17 和 IL-22 浓度，并与恩替卡韦联合使用时明显下调 AST、ALT、BATF、IL-17 和 IL-22 的表达及 Th17 细胞比例。
HBV 明显上调 BATF 表达，促进 Th17 细胞激活。相反，BATF 干扰显著抑制 Th17 细胞增殖及 IL-17 和 IL-22 分泌，减轻肝损伤。
