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Paola Di Meglio
Posters-Accepted Abstracts: J Clin Exp Dermatol Res
Psoriasis is a chronic inflammatory skin disease resulting from the interaction of genetic and environmental factors. Crosstalk between innate, adaptive and epithelial cells underpins the pathological response in this disease. More than 40 diseaseassociated loci have been identified to contribute to psoriasis. However, environmental risk factors remain less well-defined on a mechanistic basis. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that senses environmental stimuli, has been previously implicated at barrier tissue organ such as the gut as critical regulator of tissue-homeostasis. Here, the author shall present recent data showing how AhR modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists increased inflammation. Similarly, AhR signalling via the endogenous ligand FICZ reduced the inflammatory response in the Aldara-induced model of psoriasiforme skin inflammation 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 pro-inflammatory stimuli and upregulation of AP-1 family members of transcription factors. Thus, these data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory skin disorders.