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Status |
Public on Jun 11, 2014 |
Title |
Environmental factors transmitted by aryl hydrocarbon receptor influence severity of psoriatic skin inflammation [RNA-Seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is 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 upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and 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.
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Overall design |
Total RNA obtained from skin explants taken from psoriatic patients or healthy donors cultured in the presence of AhR agonist or antagonist
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Contributor(s) |
Stockinger B, Di Meglio P, Duarte JH |
Citation(s) |
24909886 |
Submission date |
Jun 14, 2013 |
Last update date |
May 15, 2019 |
Contact name |
Gitta Stockinger |
E-mail(s) |
bstocki@nimr.mrc.ac.uk
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Organization name |
National Institute for Medical Research
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Department |
Division of Molecular Immunology
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Street address |
The Ridgeway
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City |
London |
ZIP/Postal code |
NW7 1AA |
Country |
United Kingdom |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (84)
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This SubSeries is part of SuperSeries: |
GSE47965 |
Environmental factors transmitted by aryl hydrocarbon receptor influence severity of psoriatic skin inflammation |
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Relations |
BioProject |
PRJNA208430 |
SRA |
SRP026042 |