TitleInduction of regulatory T cells by green tea polyphenol EGCG.
Publication TypeJournal Article
Year of Publication2011
AuthorsWong, CP, Nguyen, LP, Noh, SK, Bray, TM, Bruno, RS, Ho, E
JournalImmunol Lett
Date Published09/2011
KeywordsAnimals, Catechin, Cell Line, Tumor, Cytokines, DNA Methylation, DNA Modification Methylases, Forkhead Transcription Factors, Gene Expression Regulation, Humans, Interleukin-10, Jurkat Cells, Male, Mice, Mice, Inbred BALB C, Polyphenols, T-Lymphocytes, T-Lymphocytes, Regulatory, Tea

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.

Alternate JournalImmunol. Lett.
PubMed ID21621552
PubMed Central IDPMC4125122
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
P30 ES00210 / ES / NIEHS NIH HHS / United States