Commensal Microbiota Regulates Skin Barrier Function And Repair Via Signaling Through The Aryl Hydrocarbon Receptor

Essential to terrestrial life is the formation of a competent skin barrier that prevents desiccation and entry by harmful substances. A tightly orchestrated series of cellular changes is required for the proper formation of the epidermal permeability barrier. These changes occur in the context of the commensal skin microbiota. Using germ free mice and antibiotic depletion models, we demonstrate the microbiota is necessary for proper differentiation and repair of the barrier. These effects were mediated by keratinocyte signaling through the aryl hydrocarbon receptor (AHR), a xenobiotic receptor that also regulates epidermal differentiation. Murine skin lacking keratinocyte AHR was more susceptible to infection by S. aureus and increased pathology in a model of atopic dermatitis. Topical colonization with a defined consortium of human skin commensals restored barrier competence in germ free skin and during epicutaneous sensitization; these effects were dependent on keratinocyte AHR. We reveal a fundamental role for the commensal skin microbiota in directing skin barrier formation and repair through the AHR, with far-reaching implications for the numerous skin disorders characterized by disrupted epidermal differentiation and/or barrier competence.