Epigenetically Mediated Pathogenic Effects of Phenanthrene on Regulatory T Cells
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 cel...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2013/967029 |
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| author | Jing Liu Luhua Zhang Lisa C. Winterroth Marco Garcia Shannon Weiman Jillian W. Wong John B. Sunwoo Kari C. Nadeau |
| author_facet | Jing Liu Luhua Zhang Lisa C. Winterroth Marco Garcia Shannon Weiman Jillian W. Wong John B. Sunwoo Kari C. Nadeau |
| author_sort | Jing Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-849f7167ba264051ab2521cb9ff40a15 |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-849f7167ba264051ab2521cb9ff40a152025-02-03T05:59:53ZengWileyJournal of Toxicology1687-81911687-82052013-01-01201310.1155/2013/967029967029Epigenetically Mediated Pathogenic Effects of Phenanthrene on Regulatory T CellsJing Liu0Luhua Zhang1Lisa C. Winterroth2Marco Garcia3Shannon Weiman4Jillian W. Wong5John B. Sunwoo6Kari C. Nadeau7Stanford University School of Medicine, Division of Immunology and Allergy, Grant Building, 3rd Floor, S370, MC5208, Stanford, CA 94305, USAStanford University School of Medicine, Division of Immunology and Allergy, Grant Building, 3rd Floor, S370, MC5208, Stanford, CA 94305, USAStanford University School of Medicine, Division of Immunology and Allergy, Grant Building, 3rd Floor, S370, MC5208, Stanford, CA 94305, USAStanford University School of Medicine, Division of Immunology and Allergy, Grant Building, 3rd Floor, S370, MC5208, Stanford, CA 94305, USAStanford University School of Medicine, Division of Immunology and Allergy, Grant Building, 3rd Floor, S370, MC5208, Stanford, CA 94305, USAStanford University School of Medicine, Division of Immunology and Allergy, Grant Building, 3rd Floor, S370, MC5208, Stanford, CA 94305, USAStanford University School of Medicine, Division of Immunology and Allergy, Grant Building, 3rd Floor, S370, MC5208, Stanford, CA 94305, USAStanford University School of Medicine, Division of Immunology and Allergy, Grant Building, 3rd Floor, S370, MC5208, Stanford, CA 94305, USAPhenanthrene (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.http://dx.doi.org/10.1155/2013/967029 |
| spellingShingle | Jing Liu Luhua Zhang Lisa C. Winterroth Marco Garcia Shannon Weiman Jillian W. Wong John B. Sunwoo Kari C. Nadeau Epigenetically Mediated Pathogenic Effects of Phenanthrene on Regulatory T Cells Journal of Toxicology |
| title | Epigenetically Mediated Pathogenic Effects of Phenanthrene on Regulatory T Cells |
| title_full | Epigenetically Mediated Pathogenic Effects of Phenanthrene on Regulatory T Cells |
| title_fullStr | Epigenetically Mediated Pathogenic Effects of Phenanthrene on Regulatory T Cells |
| title_full_unstemmed | Epigenetically Mediated Pathogenic Effects of Phenanthrene on Regulatory T Cells |
| title_short | Epigenetically Mediated Pathogenic Effects of Phenanthrene on Regulatory T Cells |
| title_sort | epigenetically mediated pathogenic effects of phenanthrene on regulatory t cells |
| url | http://dx.doi.org/10.1155/2013/967029 |
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