Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
Institute of Hepatology, Shandong University, Jinan, China.
Expert Rev Clin Immunol. 2021 Feb;17(2):177-185. doi: 10.1080/1744666X.2020.1866987. Epub 2021 Jan 13.
Methylation pattern of gene modification is essential for the differentiation of T regulatory cells (Tregs) and 5-Aza-2'-deoxycytidine is a common inhibitor of methylation. This study aimed to investigate the potential effects of Treg polarizing conditions and 5-Aza-2'-deoxycytidine treatment in the differentiation of naïve T cells during chronic hepatitis B virus (HBV) infection.
The frequency of Tregs in peripheral blood was determined by flow cytometry from patients with chronic hepatitis B (CHB) (n = 51), liver cirrhosis (LC) (n = 47), hepatocellular carcinoma (HCC) (n = 40) and healthy controls (HCs) (n = 17). Gene expression were detected by qRT-PCR and DNA methyltransferases (DNMT) Activity was also determined.
The frequency of Tregs and Foxp3 expression in peripheral blood from 5-Aza-2'-deoxycytidine-treated groups were higher than that with acetic acid treatment as a control. Foxp3 mRNA and the frequency of Tregs derived from naïve CD4T cells from peripheral blood of patients with HCC or LC were more pronounced compared with HCs. 5-Aza-2'-deoxycytidine may have induced a more pronounced upward trend of PD-1 expression in HBV patients.
5-Aza-2'-deoxycytidine mediated demethylation has potential effects on enhancing the differentiation of naïve T cells to Tregs in chronic HBV infection.
基因修饰的甲基化模式对于 T 调节细胞（Tregs）的分化至关重要，5-氮杂-2′-脱氧胞苷是一种常见的甲基化抑制剂。本研究旨在探讨 Treg 极化条件和 5-氮杂-2′-脱氧胞苷处理在慢性乙型肝炎病毒（HBV）感染期间对幼稚 T 细胞分化的潜在影响。
采用流式细胞术检测慢性乙型肝炎（CHB）（n=51）、肝硬化（LC）（n=47）、肝癌（HCC）（n=40）和健康对照（HC）（n=17）患者外周血中 Tregs 的频率。采用 qRT-PCR 检测基因表达，同时测定 DNA 甲基转移酶（DNMT）活性。
与醋酸处理作为对照相比，5-氮杂-2′-脱氧胞苷处理组外周血中 Tregs 的频率和 Foxp3 表达更高。来自 HCC 或 LC 患者外周血的幼稚 CD4T 细胞衍生的 Foxp3 mRNA 和 Tregs 频率与 HCs 相比更为明显。5-氮杂-2′-脱氧胞苷可能诱导 HBV 患者 PD-1 表达呈更明显的上升趋势。
5-氮杂-2′-脱氧胞苷介导的去甲基化对增强慢性 HBV 感染中幼稚 T 细胞向 Tregs 的分化具有潜在作用。
