Induction of regulatory T cells by green tea polyphenol EGCG

Abstract

Regulatory T cells (Treg) are critical in maintaining immune tolerance and suppressing autoimmunity. The transcription factor Foxp3 serves as a master switch that controls the development and function of Treg. Foxp3 expression is epigenetically regulated by DNA methylation, and DNA methyltransferase (DNMT) inhibitors can induce Foxp3 expression in naive CD4+ T cells. We showed that EGCG, a major green tea polyphenol, could act as a dietary DNMT inhibitor, and induced Foxp3 and IL-10 expression in CD4+ Jurkat T cells at physiologically relevant concentrations in vitro. We further showed that mice treated with EGCG in vivo had significantly increased Treg frequencies and numbers in spleen and lymph nodes and had inhibited T cell response. Induction of Foxp3 expression correlated with a concomitant reduction in DNMT expression and a decrease in global DNA methylation. Our data suggested that EGCG can induce Foxp3 expression and increase Treg frequency via a novel epigenetic mechanism. While the DNMT inhibitory effects of EGCG was not as potent as pharmacologic agents such as 5-aza-2′-deoxycytidine, the ability of dietary agents to target similar mechanisms offers opportunities for potentially sustained and longer-term exposures with lower toxicity. Our work provides the foundation for future studies to further examine and evaluate dietary strategies to modulate immune function.

Topical Application of <i>Rosa multiflora</i> Root Extract Improves Atopic Dermatitis-Like Skin Lesions Induced by Mite Antigen in NC/Nga Mice

“…26,27) Especially, more recent study explained that condensed tannins induced Foxp3 and IL-10 expression in Jurkat T cells and increased Tr1 frequencies and numbers in vivo. 28) Therefore, RM-3 might reduce oxidative stress and pro-inflammatory signaling pathway in skin allergic inflammation, and activate Treg, leads to down-regulate Th2 cytokines-mediated immune system in this study.…”

Targeting DNA Methylation with Green Tea Catechins

“…Wong et al [29] reported that EGCG, at physiologically relevant concentrations in vitro, inhibited DNMT and induced the transcription factor Foxp3. In addition, it was shown that in the in vitro culture system, EGCG also reduced the gene expression of all three DNMTs (DNMT 1, DNMT3a and DNMT3b), which correlated with reduced DNA methylation in the Jurkat T cells treated with EGCG [29].…”

Green Tea as an Agricultural Based Health Promoting Food: The Past Five to Ten Years

“…Regulatory T cells (T-reg) are essential in maintaining immune functions by targeting sites of sustained inflammation [28]. Recent in vitro and in vivo studies showed that EGCG (2-50 μM) induced T-reg via the up-regulation of Foxp3, i.e., a transcription factor regulated by DNA methylation [29]. The effect of EGCG on Foxp3 gene expression was similar to that of DNA methyltransferase inhibitors.…”