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AhR leads to reciprocal epigenetic regulation of FoxP3 and IL-17 expression and amelioration of experimental colitis

Singh, U.P.*, Narendra P. Singh*, Balwan Singh, Robert L Price, Mitzi Nagarkatti,and Prakash S. Nagarkatti. (2011) Activation of Aryl Hydrocarbon Receptor Leads to Reciprocal Epigenetic Regulation of FoxP3 and IL-17 genes and Amelioration of Experimental Colitis. (Accepted in PLoS ONE).

Abstract

Background: Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3(+) Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis.
Methodology/principal findings: Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD.

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