Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis

Abstract

The aryl hydrocarbon receptor (AHR)/AHR-nuclear translocator (ARNT) system is a sensitive sensor for small molecular, xenobiotic chemicals of exogenous and endogenous origin, including dioxins, phytochemicals, microbial bioproducts, and tryptophan photoproducts. AHR/ARNT are abundantly expressed in the skin. Once activated, the AHR/ARNT axis strengthens skin barrier functions and accelerates epidermal terminal differentiation by upregulating filaggrin expression. In addition, AHR activation induces oxidative stress. However, some AHR ligands simultaneously activate the nuclear factor-erythroid 2-related factor-2 (NRF2) transcription factor, which is a master switch of antioxidative enzymes that neutralizes oxidative stress. The immunoregulatory system governing T-helper 17/22 (Th17/22) and T regulatory cells (Treg) is also regulated by the AHR system. Notably, AHR agonists, such as tapinarof, are currently used as therapeutic agents in psoriasis and atopic dermatitis. In this review, we summarize recent topics on AHR related to atopic dermatitis and psoriasis.

Air Pollution and Atopic Dermatitis (AD): The Impact of Particulate Matter (PM10) on an AD Mouse-Model

“…Three important groups of genes are targeted by AHR [ 29 ]. First, a battery of genes encoding detoxifying enzymes (xenobiotic metabolizing enzymes, XMEs ), such as the cytochrome P450 (CYP) gene CYP1A1 (Phase I XME) and Phase II enzymes (NADPH dehydrogenase quinone 1, NQO1 ; glutathione S-transferases, GSTA2 ; uridine 5-diphospho-glucuronosyltransferases; UGT1A1 , UGT1A6 , UGT1A7 ) [ 31 , 32 , 33 ]; second, genes related to epidermal differentiation and skin barrier integrity; and finally, genes related to immunity.…”

“…Xenobiotic small chemicals have strong affinity to AHR and cause persistent activation of the receptor [ 28 ]. The pathogenic implication of AHR and its gene polymorphism in AD remain elusive but it has been suggested that most AHRs lack physiological ligands in the Th2-prone milieu in AD [ 31 , 34 ].…”

New Treatment Addressing the Pathogenesis of Psoriasis

“…Endogenous and exogenous molecules and dioxins are known as ligands of AhR [ 57 , 58 ]. AhR activation induces oxidative stress through CYP1A1 and neutralizes oxidative stress through the nuclear factor-erythroid 2-related factor-2 (NRF2) transcription factor [ 59 ]. Furthermore, AhR regulates the balance of the Th17/22 system, which is important for developing psoriasis [ 59 ].…”

“…AhR activation induces oxidative stress through CYP1A1 and neutralizes oxidative stress through the nuclear factor-erythroid 2-related factor-2 (NRF2) transcription factor [ 59 ]. Furthermore, AhR regulates the balance of the Th17/22 system, which is important for developing psoriasis [ 59 ]. AhR agonists decreased IL-23 receptor, Th17 master transcription factor retinoic acid-related orphan receptor C (RORC) and the number of Th17 cells [ 60 ].…”

Emerging Therapeutic Options for Chronic Pruritus

“…AhR, also termed dioxin receptor, is a ligand-activated transcription factor expressed in all types of skin cells, which binds to environmental polyaromatic hydrocarbons and dioxins, eventually causing oxidative stress [207,208]. There is high expression of AhR in all epidermal cells and fibroblasts of the skin [209].…”