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5-氮杂-2'-脱氧胞苷可能会增加慢性乙型肝炎病毒感染患者外周血 CD4 初始 T 细胞中 T 调节细胞的频率。

5-Aza-2'-deoxycytidine may enhance the frequency of T regulatory cells from CD4 naïve T cells isolated from the peripheral blood of patients with chronic HBV infection.

机构信息

Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.

Institute of Hepatology, Shandong University, Jinan, China.

出版信息

Expert Rev Clin Immunol. 2021 Feb;17(2):177-185. doi: 10.1080/1744666X.2020.1866987. Epub 2021 Jan 13.

Abstract

OBJECTIVES

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.

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-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.

CONCLUSIONS

5-Aza-2'-deoxycytidine mediated demethylation has potential effects on enhancing the differentiation of naïve T cells to Tregs in chronic HBV infection.

摘要

目的

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。

方法

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。

结果

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。

结论

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。

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