ABSTRACT

Objectives

Methylation pattern of gene modification is essential for the differentiation of T regulatory cells (Tregs) and 5-Aza-2ʹ-deoxycytidine is a common inhibitor of methylation. This study aimed to investigate the potential effects of Treg polarizing conditions and 5-Aza-2ʹ-deoxycytidine treatment in the differentiation of naïve T cells during chronic hepatitis B virus (HBV) infection.

Methods

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.

Results

The frequency of Tregs and Foxp3 expression in peripheral blood from 5-Aza-2ʹ-deoxycytidine-treated groups were higher than that with acetic acid treatment as a control. Foxp3 mRNA and the frequency of Tregs derived from naïve CD4⁺T cells from peripheral blood of patients with HCC or LC were more pronounced compared with HCs. 5-Aza-2ʹ-deoxycytidine may have induced a more pronounced upward trend of PD-1 expression in HBV patients.

Conclusions

5-Aza-2ʹ-deoxycytidine mediated demethylation has potential effects on enhancing the differentiation of naïve T cells to Tregs in chronic HBV infection.

中文翻译：

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5-Aza-2'-脱氧胞苷可提高从慢性 HBV 感染患者外周血中分离的 CD4+ 幼稚 T 细胞中 T 调节细胞的频率

摘要

目标

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-Aza-2ʹ-脱氧胞苷是一种常见的甲基化抑制剂。本研究旨在研究 Treg 极化条件和 5-Aza-2ʹ-脱氧胞苷治疗对慢性乙型肝炎病毒 (HBV) 感染期间幼稚 T 细胞分化的潜在影响。

方法

外周血中 Tregs 的频率由慢性乙型肝炎 (CHB) (n = 51)、肝硬化 (LC) (n = 47)、肝细胞癌 (HCC) (n = 40) 和健康患者的流式细胞仪测定。对照（HC）（n = 17）。通过 qRT-PCR 检测基因表达，并测定 DNA 甲基转移酶 (DNMT) 活性。

结果

5-Aza-2ʹ-脱氧胞苷处理组外周血中Tregs和Foxp3的表达频率高于乙酸处理组。Foxp3 mRNA 和来自HCC 或 LC 患者外周血幼稚 CD4 ⁺ T 细胞的 Treg 频率比 HC 更明显。5-Aza-2ʹ-脱氧胞苷可能在 HBV 患者中诱导了更明显的 PD-1 表达上升趋势。

结论

5-Aza-2ʹ-脱氧胞苷介导的去甲基化对促进慢性HBV感染中幼稚T细胞向Tregs的分化具有潜在作用。