Cited by 1,634Psoriasis: Treatment and PathogenesisT-cell and B-cell ImmunologyImmunotoxicology and immune responses

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

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Veldhoen, Marc, Hirota, Keiji, Westendorf, Astrid M., Buer, Jan, Dumoutier, Laure, Renauld, Jean-Christophe, Stockinger, Brigitta·2008·Nature

DOI 10.1038/nature06881

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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.

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Authors: Veldhoen, M., Hirota, K., Westendorf, A. M., Buer, J., Dumoutier, L., Renauld, J.-C., & Stockinger, B.
Affiliations: National Institute for Medical Research (GB)
Essen University Hospital (DE)
Ludwig Cancer Research (BE)
Corresponding author: Stockinger, Brigitta
ORCID: Veldhoen, Marc
Hirota, Keiji
Westendorf, Astrid M.
Buer, Jan
Dumoutier, Laure
Renauld, Jean-Christophe
Stockinger, Brigitta
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2008-03-23
Volume: 453
Issue: 7191
Pages: 106-109
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature06881
OpenAlex: W1993003564
Cited by: 1,634
References: 31
Citations by year: 2026: 33 · 2025: 44 · 2024: 49 · 2023: 54 · 2022: 87 · 2021: 94 · 2020: 96 · 2019: 90 · 2018: 96 · 2017: 93 · 2016: 96 · 2015: 82 · 2014: 114 · 2013: 107 · 2012: 118
FWCI: 52.43
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
HZI (Helmholtz Centre for Infection Research) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
DIAL (Catholic University of Leuven) (submittedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: University of Leicester
Topics: Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Keywords: aryl hydrocarbon receptor, Th17 cells, autoimmunity, environmental toxins, IL-22, experimental autoimmune encephalitis, multiple sclerosis, regulatory T cells, CD4+ T cells, immunomodulation, AhR ligands, dioxins, IL-17
MeSH terms: Interleukin-22, Animals, Cell Differentiation, Cells, Cultured, Encephalomyelitis, Autoimmune, Experimental, Environmental Exposure, Environmental Pollutants, T-Lymphocytes, Helper-Inducer, Humans, Interleukins, Ligands, Mice, Inbred C57BL, Transduction, Genetic, Hazardous Substances, Autoimmunity, Receptors, Aryl Hydrocarbon, Interleukin-17, Mice

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

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