Can the Aryl Hydrocarbon Receptor Unlock New Treatments for Chronic Inflammatory Skin Diseases?

by Haroon Ahmad, MD 2025-01-01 00:00

PhysicianMedical

🔍 Key Finding The aryl hydrocarbon receptor (AHR) plays a multifaceted role in inflammatory skin diseases like psoriasis, atopic dermatitis, acne, and hidradenitis suppurativa, influencing skin barrier function, immune responses, and inflammation, making it a potential therapeutic target. Modulating AHR activity, such as with the FDA-approved tapinarof for psoriasis, shows promise for treating these conditions by reducing inflammation and restoring skin homeostasis.

🔬 Methodology Overview

Design: Narrative review
Data Sources: Published literature
Selection Criteria: Studies investigating the role of the aryl hydrocarbon receptor (AHR) in chronic inflammatory skin diseases, including psoriasis, atopic dermatitis, acne, hidradenitis suppurativa, and vitiligo.
Analysis Approach: Qualitative synthesis of findings from in vitro studies, in vivo animal models, and human clinical trials.
Scope: Overview of AHR signaling pathways, AHR’s role in skin physiology and pathology, and the therapeutic potential of AHR modulators in dermatological conditions.

📊 Results

Psoriasis: AHR-deficient mice in an imiquimod-induced psoriasis model showed increased psoriasiform skin inflammation and higher IL-17 and IL-22 production compared to controls.
Psoriasis: Tapinarof, an AHR agonist, has been FDA-approved for plaque psoriasis in adults and shown to reduce IL-17 and IL-22 in Th17 cells.
Hidradenitis Suppurativa (HS): Expression of AHR target genes (AHRR, CYP1A1, and CYP1A2) was significantly lower in HS patients compared to healthy controls. Levels of the AHR agonist IAA (indole-3-acetic acid), produced by skin microbiota, were also lower in HS patients.
Acne: AHR activation has been shown to both increase and decrease sebum production in different studies, suggesting a complex role. A study of 100 participants (70 with acne, 30 healthy controls) found significantly increased AHR gene expression in those with acne, correlating with disease severity.
Atopic Dermatitis (AD): Exposure to air pollution (specifically particulate matter) and tobacco smoke, both containing AHR-activating pollutants like PAHs, has been linked to increased AD risk and symptom severity. Coal tar, containing PAHs, has shown some efficacy in AD treatment, potentially through AHR activation.
Vitiligo: A study of 40 participants (20 with vitiligo, 20 healthy controls) found reduced AHR expression in CD4+ T cells and skin of vitiligo patients, along with increased IL-17A and IL-22 levels. AHR suppression further increased IL-17A and decreased IL-22 in vitiligo patients’ CD4+ T cells. A case report showed repigmentation in a vitiligo patient after off-label tapinarof treatment.

💡 Clinical Impact AHR modulation, particularly by tapinarof, offers a promising new therapeutic avenue for chronic inflammatory skin diseases like psoriasis, atopic dermatitis, hidradenitis suppurativa, acne, and vitiligo, potentially improving treatment outcomes by targeting inflammation, immune dysregulation, and skin barrier function. Further research, including randomized controlled trials, is needed to fully elucidate AHR’s role in these diseases and optimize treatment strategies using AHR modulators.

🤔 Limitations

Limited long-term safety data for tapinarof.
Limited understanding of the precise mechanisms by which AHR contributes to psoriasis.
Limited understanding of the exact processes by which AHR is implicated in hidradenitis suppurativa (HS).
Limited research on the precise processes underlying AHR signalling in acne.
Excessive expression of AHR can contribute to the development of atopic dermatitis (AD).
Limited clinical investigations on tapinarof for vitiligo.
Acne is a multifaceted disorder influenced by a range of factors beyond AHR.

✨ What It Means For You This review highlights the aryl hydrocarbon receptor (AHR) as a potential therapeutic target in chronic inflammatory skin diseases like psoriasis, hidradenitis suppurativa, acne, atopic dermatitis, and vitiligo. Doctors should consider AHR modulation as a therapeutic strategy for these conditions, with further research needed to fully elucidate AHR’s role and develop targeted therapies like tapinarof, which shows promise in psoriasis and potentially other AHR-related skin disorders.

Reference Dec M, Arasiewicz H. Aryl hydrocarbon receptor role in chronic inflammatory skin diseases: a narrative review. Adv Dermatol Allergol. 2024;41:9-19. https://doi.org/10.5114/ada.2023.135617