Role of Aryl Hydrocarbon Receptor Activation in Inflammatory Chronic Skin Diseases

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.

Keywords: acne; aryl hydrocarbon receptor; atopic dermatitis; hidradenitis suppurativa; psoriasis.

Figure 1

Canonical and non-canonical signaling pathways activated by AhR. In canonical pathways upon ligand-binding by either exogenous or endogenous agonists, AhR undergoes conformational changes leading to the dissociation of p23 and XAP2 with consequent translocation in the nucleus and formation of a AhR:ARNT heterodimer. The AhR:ARNT complex binds to upstream regulatory regions of its target genes which contain canonical aryl hydrocarbon XRE elements. In non-canonical pathway ligand-AhR complex can interact directly with sites distinct from the consensus XRE.