Xenobiotic Receptors and Their Mates in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is the most common inflammatory skin disease worldwide. It is a chronic, relapsing and pruritic skin disorder which results from epidermal barrier abnormalities and immune dysregulation, both modulated by environmental factors. AD is strongly associated with asthma and allergic rhinitis in the so-called ‘atopic march.’ Xenobiotic receptors and their mates are ligand-activated transcription factors expressed in the skin where they control cellular detoxification pathways. Moreover, they regulate the expression of genes in pathways involved in AD in epithelial cells and immune cells. Activation or overexpression of xenobiotic receptors in the skin can be deleterious or beneficial, depending on context, ligand and activation duration. Moreover, their impact on skin might be amplified by crosstalk among xenobiotic receptors and their mates. Because they are activated by a broad range of endogenous molecules, drugs and pollutants owing to their promiscuous ligand affinity, they have recently crystalized the attention of researchers, including in dermatology and especially in the AD field. This review examines the putative roles of these receptors in AD by critically evaluating the conditions under which the proteins and their ligands have been studied. This information should provide new insights into AD pathogenesis and ways to develop new therapeutic interventions.

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

“…Since all PPARs are widely expressed in human skin and its appendages, there is increasing interest in their role in maintaining cutaneous homeostasis and in dermatological disorders . PPAR‐mediated signalling has attracted special interest in psoriasis, atopic dermatitis, acne, skin ageing, scleroderma, melasma, lipodystrophy and skin cancer . In the context of this Focus Theme Issue , this development encourages one to also take a closer look at why and how exactly PPARs are of special interest in a translational hair research context, with a strict focus on their best‐investigated isoform, PPAR‐γ.…”

“…[91] The possibility to harness the anti-inflammatory effects of PPAR-γ agonists to treat several inflammatory skin conditions (eg psoriasis, atopic dermatitis, acne) has been examined before. [9,13,14,17] N-Acetyl-GED-0507-34-Levo that showed beneficial effects on the HF bulge cells also possesses anti-inflammatory…”

“…Recently, we have revealed that LPP treated HFs ex vivo with N‐Acetyl‐GED‐0507‐34‐Levo show less CD8+ T‐cells, and MHC class II+ cells in and around the bulge . The possibility to harness the anti‐inflammatory effects of PPAR‐γ agonists to treat several inflammatory skin conditions (eg psoriasis, atopic dermatitis, acne) has been examined before .…”

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

“…We found that 52/304 XPGs were differentially expressed ( P < 0 .05) in skin of SPF and GF mice, and the majority were upregulated in SPF mice (n=43/52; Table S5 ). The pregnane X receptor (PXR , NR1I2 ), constitutive androstane receptor (CAR, NR1I3 ), peroxisome proliferator-activated receptor-alpha (PPARa) and aryl hydrocarbon receptor (AHR) are key transcription factors that regulate xenobiotic processing in skin [51]. Of these, only the AHR gene was differentially expressed and was upregulated in SPF skin compared to GF skin.…”

Study of associations of haplotypes of FLG gene polymorphism with the development of chronic true eczema in men

“…Экзема -острое или хроническое рецидивирующее аллергическое заболевание кожи, формирующееся под влиянием экзогенных и эндогенных триггерных факторов и характеризующееся появлением полиморфной сыпи, острой воспалительной реакцией, обусловленной серозным воспалением кожи, и сильным зудом [1]. Среди населения мира распространенность данной патологии составляет 10-20% [2,3]. При этом встречаемость экземы в странах Западной Европы выше, чем в странах Восточной Европы, Африки, Центральной Азии и Китае [4].…”