The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins
Open accessAbstract
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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Expression of IL-22 requires AhR.
“it was demonstrated that expression of IL-22 requires the AhR (Martin et al., 2009; Veldhoen et al., 2008).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Veldhoen et al., 2008
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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
- Venue
- Nature
- Published
- 2008-03-23
- Volume
- 453
- Issue
- 7191
- Pages
- 106-109
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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