Vitamin C supports conversion of human ?? T cells into FOXP3-expressing regulatory cells by epigenetic regulation.

ABSTRACT: Human ?? T cells are potent cytotoxic effector cells, produce a variety of cytokines, and can acquire regulatory activity. Induction of FOXP3, the key transcription factor of regulatory T cells (Treg), by TGF-? in human V?9?V?2?T cells has been previously reported. Vitamin C is an antioxidant and acts as multiplier of DNA hydroxymethylation. Here we have investigated the effect of the more stable phospho-modified Vitamin C (pVC) on TGF-?-induced FOXP3 expression and the resulting regulatory activity of highly purified human V?9?V?2?T cells. pVC significantly increased the TGF-?-induced FOXP3 expression and stability and also increased the suppressive activity of V?9?V?2?T cells. Importantly, pVC induced hypomethylation of the Treg-specific demethylated region (TSDR) in the FOXP3 gene. Genome-wide methylation analysis by Reduced Representation Bisulfite Sequencing additionally revealed differentially methylated regions in several important genes upon pVC treatment of ?? T cells. While Vitamin C also enhances effector functions of V?9?V?2?T cells in the absence of TGF-?, our results demonstrate that pVC potently increases the suppressive activity and FOXP3 expression in TGF-?-treated V?9?V?2?T cells by epigenetic modification of the FOXP3 gene.

SUBMITTER: Kouakanou L 

PROVIDER: S-EPMC7162875 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature