Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions

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. Ah...

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Main Authors:	Di Meglio, Paola, Duarte, João H., Ahlfors, Helena, Owens, Nick D.L., Li, Ying, Villanova, Federica, Tosi, Isabella, Hirota, Keiji, Nestle, Frank O., Mrowietz, Ulrich, Gilchrist, Michael J., Stockinger, Brigitta
Format:	Online
Language:	English
Published:	Cell Press 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067745/

id	pubmed-4067745
recordtype	oai_dc
spelling	pubmed-40677452014-06-25 Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions Di Meglio, Paola Duarte, João H. Ahlfors, Helena Owens, Nick D.L. Li, Ying Villanova, Federica Tosi, Isabella Hirota, Keiji Nestle, Frank O. Mrowietz, Ulrich Gilchrist, Michael J. Stockinger, Brigitta Article 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. Cell Press 2014-06-19 /pmc/articles/PMC4067745/ /pubmed/24909886 http://dx.doi.org/10.1016/j.immuni.2014.04.019 Text en © 2014 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Di Meglio, Paola Duarte, João H. Ahlfors, Helena Owens, Nick D.L. Li, Ying Villanova, Federica Tosi, Isabella Hirota, Keiji Nestle, Frank O. Mrowietz, Ulrich Gilchrist, Michael J. Stockinger, Brigitta
spellingShingle	Di Meglio, Paola Duarte, João H. Ahlfors, Helena Owens, Nick D.L. Li, Ying Villanova, Federica Tosi, Isabella Hirota, Keiji Nestle, Frank O. Mrowietz, Ulrich Gilchrist, Michael J. Stockinger, Brigitta Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions
author_facet	Di Meglio, Paola Duarte, João H. Ahlfors, Helena Owens, Nick D.L. Li, Ying Villanova, Federica Tosi, Isabella Hirota, Keiji Nestle, Frank O. Mrowietz, Ulrich Gilchrist, Michael J. Stockinger, Brigitta
author_sort	Di Meglio, Paola
title	Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions
title_short	Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions
title_full	Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions
title_fullStr	Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions
title_full_unstemmed	Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions
title_sort	activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions
description	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.
publisher	Cell Press
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067745/
_version_	1612105040134144000

Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions

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