Epigenetically mediated pathogenic effects of phenanthrene on regulatory T cells.
Epigenetically mediated pathogenic effects of phenanthrene on regulatory T cells.
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DOI：
10.1155/2013/967029
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发表时间：
2013
影响因子：
2.9
通讯作者：
Nadeau KC
中科院分区：
文献类型：
--
作者：
Liu J;Zhang L;Winterroth LC;Garcia M;Weiman S;Wong JW;Sunwoo JB;Nadeau KC
菲（Phe）是一种多环芳烃（PAH），是城市大气污染的主要成分。关于其他AhR配体2，3，7，8-四氯二苯并-p-二恶英（TCDD）和6-甲酰吲哚并[3，2-B]咔唑（FICZ）在修饰调节性T细胞群（Treg）或辅助性T细胞（Th）17分化中的作用，存在相互矛盾的结果，并且Phe的作用尚未充分研究。我们假设PAH的不同化学实体通过FOXP 3的表观遗传修饰诱导Treg成为Th 2或Th 17效应T细胞。为了确定菲对T细胞群的特异性影响，用Phe、TCDD或FICZ处理原代人Treg，并评估其功能、基因表达和表型。FOXP 3基因座内CpG位点的甲基化降低FOXP 3表达，导致经Phe处理的细胞中Treg功能受损并将Treg转化为CD 4 + CD 25 lo Th 2表型。相反，TCDD治疗导致IL-17 A的表观遗传修饰和Treg向Th 17 T细胞的转化。这些发现提出了一种机制，通过该机制暴露于AhR配体介导人类T细胞反应，并开始阐明环境暴露，免疫调节和人类疾病的起始之间的关系。
Phenanthrene (Phe), a polycyclic aromatic hydrocarbon (PAH), is a major constituent of urban air pollution. There have been conflicting results regarding the role of other AhR ligands 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and 6-formylindolo [3,2-b]carbazole (FICZ) in modifying regulatory T cell populations (Treg) or T helper (Th)17 differentiation, and the effects of Phe have been understudied. We hypothesized that different chemical entities of PAH induce Treg to become either Th2 or Th17 effector T cells through epigenetic modification of FOXP3. To determine specific effects on T cell populations by phenanthrene, primary human Treg were treated with Phe, TCDD, or FICZ and assessed for function, gene expression, and phenotype. Methylation of CpG sites within the FOXP3 locus reduced FOXP3 expression, leading to impaired Treg function and conversion of Treg into a CD4+CD25lo Th2 phenotype in Phe-treated cells. Conversely, TCDD treatment led to epigenetic modification of IL-17A and conversion of Treg to Th17 T cells. These findings present a mechanism by which exposure to AhR-ligands mediates human T cell responses and begins to elucidate the relationship between environmental exposures, immune modulation, and initiation of human disease.