title: Aryl Hydrocarbon Receptor in Keratinocytes Is Essential for Murine Skin Barrier Integrity.
abstract: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in adaptive cell functions, and it is highly active in the epidermis. AhR ligands can accelerate keratinocyte differentiation, but the precise role of AhR in the skin barrier is unknown. Our study showed that transepidermal water loss, a parameter of skin barrier integrity, is high in AhR-deficient mice. Experiments with conditionally AhR-deficient mouse lines identified keratinocytes as the primary cell population responsible for high transepidermal water loss. Electron microscopy showed weaker intercellular connectivity in the epidermis of keratinocytes in AhR-knockout mice, and gene expression analysis identified many barrier-associated genes as AhR targets. Moreover, AhR-deficient mice had higher interindividual differences in their microbiome. Interestingly, removing AhR ligands from the diet of wild-type mice mimicked AhR deficiency with respect to the impaired barrier; conversely, re-addition of the plant-derived ligand indole-3-carbinol rescued the barrier deficiency even in aged mice. Our results suggest that functional AhR expression is critical for skin barrier integrity and that AhR represents a molecular target for the development of therapeutic approaches for skin barrier diseases, including by dietary intervention.
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Haas
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Weighardt
authors.affiliation: Biological and Medical Research - Genomics and Transcriptomics Laboratory, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Deenen
authors.affiliation: Biological and Medical Research - Genomics and Transcriptomics Laboratory, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Köhrer
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Clausen
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, La Jolla, California, USA.
authors.forename: Sonja
authors.initials: S
authors.lastname: Zahner
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Boukamp
authors.affiliation: Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany. Electronic address: chesser@uni-duesseldorf.de.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Esser
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015603:Keratinocytes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis / Q000235:genetics*; D012871:Skin Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D018336:Receptors, Aryl Hydrocarbon; C484722:Ahr protein, mouse