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The 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 highly active in the epidermis. AhR-ligands can accelerate keratinocyte differentiation, but a precise role for AhR in the skin barrier is unknown. We here show that transepidermal water loss (TEWL), a parameter of skin barrier integrity, is high in AhR-deficient (AhR-KO) mice. Experiments with conditionally AhR-deficient mouse lines identified keratinocytes as the major responsible cell population for high TEWL. Electron microscopy showed weaker inter-cellular connectivity in the epidermis of keratinocytes in AhR-KO mice, and gene expression analysis identified many barrier-associated genes as AhR targets. Moreover, AhR-deficient mice had higher inter-individual differences in their microbiome. Interestingly, removing AhR-ligands from the diet of wild-type mice mimicked AhR-deficiency regarding the impaired barrier. Vice versa, re-addition of the plant-derived ligand indole-3-carbinol (I3C) 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 novel therapeutic approaches for skin barrier diseases, including dietary intervention.

ORGANISM(S): Mus musculus

PROVIDER: GSE80273 | GEO | 2016/08/31

SECONDARY ACCESSION(S): PRJNA318465

REPOSITORIES: GEO

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