The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins.

2.50
Hdl Handle:
http://hdl.handle.net/10033/30394
Title:
The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins.
Authors:
Veldhoen, Marc; Hirota, Keiji; Westendorf, Astrid M; Buer, Jan; Dumoutier, Laure; Renauld, Jean-Christophe; Stockinger, Brigitta
Abstract:
The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor best known for mediating the toxicity of dioxin. Environmental factors are believed to contribute to the increased prevalence of autoimmune diseases, many of which are due to the activity of T(H)17 T cells, a new helper T-cell subset characterized by the production of the cytokine IL-17. Here we show that in the CD4+ T-cell lineage of mice AHR expression is restricted to the T(H)17 cell subset and its ligation results in the production of the T(H)17 cytokine interleukin (IL)-22. AHR is also expressed in human T(H)17 cells. Activation of AHR by a high-affinity ligand during T(H)17 cell development markedly increases the proportion of T(H)17 T cells and their production of cytokines. CD4+ T cells from AHR-deficient mice can develop T(H)17 cell responses, but when confronted with AHR ligand fail to produce IL-22 and do not show enhanced T(H)17 cell development. AHR activation during induction of experimental autoimmune encephalomyelitis causes accelerated onset and increased pathology in wild-type mice, but not AHR-deficient mice. AHR ligands may therefore represent co-factors in the development of autoimmune diseases.
Affiliation:
Division of Molecular Immunology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK.
Citation:
The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. 2008, 453 (7191):106-9 Nature
Journal:
Nature
Issue Date:
1-May-2008
URI:
http://hdl.handle.net/10033/30394
DOI:
10.1038/nature06881
PubMed ID:
18362914
Type:
Article
Language:
en
ISSN:
1476-4687
Appears in Collections:
Publications of Dept. Cell Biology (ZB)

Full metadata record

DC FieldValue Language
dc.contributor.authorVeldhoen, Marc-
dc.contributor.authorHirota, Keiji-
dc.contributor.authorWestendorf, Astrid M-
dc.contributor.authorBuer, Jan-
dc.contributor.authorDumoutier, Laure-
dc.contributor.authorRenauld, Jean-Christophe-
dc.contributor.authorStockinger, Brigitta-
dc.date.accessioned2008-06-24T12:14:28Z-
dc.date.available2008-06-24T12:14:28Z-
dc.date.issued2008-05-01-
dc.identifier.citationThe aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. 2008, 453 (7191):106-9 Natureen
dc.identifier.issn1476-4687-
dc.identifier.pmid18362914-
dc.identifier.doi10.1038/nature06881-
dc.identifier.urihttp://hdl.handle.net/10033/30394-
dc.description.abstractThe aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor best known for mediating the toxicity of dioxin. Environmental factors are believed to contribute to the increased prevalence of autoimmune diseases, many of which are due to the activity of T(H)17 T cells, a new helper T-cell subset characterized by the production of the cytokine IL-17. Here we show that in the CD4+ T-cell lineage of mice AHR expression is restricted to the T(H)17 cell subset and its ligation results in the production of the T(H)17 cytokine interleukin (IL)-22. AHR is also expressed in human T(H)17 cells. Activation of AHR by a high-affinity ligand during T(H)17 cell development markedly increases the proportion of T(H)17 T cells and their production of cytokines. CD4+ T cells from AHR-deficient mice can develop T(H)17 cell responses, but when confronted with AHR ligand fail to produce IL-22 and do not show enhanced T(H)17 cell development. AHR activation during induction of experimental autoimmune encephalomyelitis causes accelerated onset and increased pathology in wild-type mice, but not AHR-deficient mice. AHR ligands may therefore represent co-factors in the development of autoimmune diseases.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshAutoimmunityen
dc.subject.meshCell Differentiationen
dc.subject.meshCells, Cultureden
dc.subject.meshEncephalomyelitis, Autoimmune, Experimentalen
dc.subject.meshEnvironmental Exposureen
dc.subject.meshEnvironmental Pollutantsen
dc.subject.meshHazardous Substancesen
dc.subject.meshHumansen
dc.subject.meshInterleukin-17en
dc.subject.meshInterleukinsen
dc.subject.meshLigandsen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshReceptors, Aryl Hydrocarbonen
dc.subject.meshT-Lymphocytes, Helper-Induceren
dc.subject.meshTransduction, Geneticen
dc.titleThe aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins.en
dc.typeArticleen
dc.contributor.departmentDivision of Molecular Immunology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK.en
dc.identifier.journalNatureen

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