196 Aryl hydrocarbon receptor ligand leflunomide exerts triple action to dampen the inflammatory skin disease atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease in which patients suffer from red, itching lesions. Current therapeutics target disease-associated immune cells but neglect local skin-specific factors AD and are not suitable for the majority of mild to moderate adult pediatric patients. AHR activation has been described reverse pathology increasingly recognized as new therapeutic target. We use approved drug leflunomide activate aim gather biological evidence repositioning treatment AD. Therefore, primary human keratinocytes were grown into 3D epidermal equivalents stimulated with IL-4 mimic They treated TCDD, (AHR activators) leflunomide’s metabolite teriflunomide (not activating AHR) harvested genome-wide transcriptomic protein expression analysis. find normalize hyperproliferation, restoring barrier, normalizing antimicrobial peptide dampening signaling. Mutations FLG gene strongly affected keratinocyte response IL-4, yet responsiveness. In conclusion, this study shows complete profile agonist dependent under conditions keratinocytes. demonstrate potential through triple action against by proliferation rates, improving barrier function This opens avenues repurposing topical diseases.