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.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this manuscript.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
All authors have made contributions to the study and approved the publication. Yu Fang, Xiao-Dong Yuan and Hui-Hui Liu contributed to the majority of the experiments and data collection. Lin Xiang and La-Mei Chen and Shuai Gao completed statistical analysis and interpretation of data. Yu-Chen Fan and Kai Wang and contributed to the study designed and drafted the manuscript. Yu-Chen Fan and Yu Fang contributed to revised the manuscript. Kai Wang was responsible for study supervision and obtaining funding.