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Immunity. 2014 Jun 19;40(6):989-1001. doi: 10.1016/j.immuni.2014.04.019. Epub 2014 Jun 5.

Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.

Author information

1
Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
2
Division of Systems Biology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
3
St. John's Institute of Dermatology, King's College London and NIHR Biomedical Research Centre, London SE1 9RT, UK.
4
Psoriasis Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
5
Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. Electronic address: bstocki@nimr.mrc.ac.uk.

Abstract

Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanisms are largely unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists increased inflammation. Similarly, AhR signaling via the endogenous ligand FICZ reduced the inflammatory response in the imiquimod-induced model of skin inflammation and AhR-deficient mice exhibited a substantial exacerbation of the disease, compared to AhR-sufficient controls. Nonhematopoietic cells, in particular keratinocytes, were responsible for this hyperinflammatory response, which involved upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders.

PMID:
24909886
PMCID:
PMC4067745
DOI:
10.1016/j.immuni.2014.04.019
[Indexed for MEDLINE]
Free PMC Article

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