Abstract
Aryl Hydrocarbon Receptor (AhR) is an evolutionary transcription factor which acts as a crucial sensor of different exogenous and endogenous molecules Recent data indicate that AhR is implicated in several physiological processes such as cell physiology, host defense, proliferation and differentiation of immune cells, and detoxification. Moreover, AhR involvement has been reported in the development and maintenance of several pathological conditions. In recent years, an increasing number of studies have accumulated highlighting the regulatory role of AhR in the physiology of the skin. However, there is evidence of both beneficial and harmful effects of AHR signaling. At present, most of the evidence concerns inflammatory skin diseases, in particular atopic dermatitis, psoriasis, acne, and hidradenitis suppurativa. This review exam-ines the role of AhR in skin homeostasis and the therapeutic implication of its pharmacological modulation in these cutaneous inflammatory diseases.
Highlights
Aryl Hydrocarbon Receptor (AhR), a ligand-dependent transcription factor, is known to mediate the biochemical and toxic effects of xenobiotics, environmental stresses, endogenous ligands, microbial-derived products, and physiological compounds such as tryptophan derivatives [1,2,3,4,5]
To exert its role at transcriptional level, AhR forms a heterodimer with its Class II partner Aryl Hydrocarbon Receptor Nucleus Translocator (ARNT), recognizing a specific Xenobiotic Response Element (XRE, or DRE for Dioxin Response Element) in the promoter of downstream genes [15]
Upon ligand-binding by either exogenous or endogenous agonists, AhR undergoes conformational changes leading to the dissociation of p23 and XAP2, the unmasking of Nuclear Localization Signal (NLS), and the consequent translocation in the nucleus through the interaction with importin β [15]
Summary
Aryl Hydrocarbon Receptor (AhR), a ligand-dependent transcription factor, is known to mediate the biochemical and toxic effects of xenobiotics, environmental stresses, endogenous ligands, microbial-derived products, and physiological compounds such as tryptophan derivatives [1,2,3,4,5]. Recent data indicate that AhR is implicated in several physiological processes such as xenobiotic metabolism, cell cycle regulation, reproduction, development, and immune response, by playing a pivotal role in signaling networks [5,6,7]. AhR signaling appears to play an important role in maintaining skin homeostasis by regulating metabolism of environmental toxins, oxidative stress, photoinduced response, keratinocytes differentiation, epidermal barrier function, melanogenesis, and skin immune network [8,9,10]. Expression of genes encoding FLG, LOR, IVL, and other barrier-related proteins in the EDC loci Up-regulation of OVOL1 transcription factor important for the epidermal differentiation AHR axis activation inhibits the IL-13/IL-4-mediated STAT6 phosphorylation and restores the IL-13/IL-4-mediated FLG decrease Induction of ARTN gene expression. We performed a narrative review of the international literature regarding the role of AhR and therapeutic implication of its pharmacological modulation in some skin diseases
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