A Hero Revealed: Targeting the AHR for treatment of inflammatory skin diseases

With this research, we aimed to increase our understanding of the role of AHR signaling in the formation and maintenance of the epidermal barrier. We focused on the regulation of keratinocyte proliferation and differentiation and investigated the potential of novel ligands as therapeutics to restore epidermal homeostasis in inflammatory skin diseases.

Novel therapeutic ligands were analyzed in vitro and in vivo. We studied the capability of these AHR ligands in inflammatory skin models to restore aberrant keratinocyte differentiation and proliferation as well as dampen inflammatory signaling. 
To discover novel AHR-targeting therapeutics it is important to understand the mechanism behind AHR signaling. We studied the mechanism of AHR-driven keratinocyte differentiation and elucidated novel interaction partners through which the AHR directs terminal differentiation. We furthermore developed a method to knock out genes in a keratinocyte cell line using CRISPR/Cas9 as well as a novel method to measure skin barrier function. To assess the importance of AHR signaling in the inflammatory response of keratinocyte towards disease-associated cytokines, the effects of AHR activation upon experimental skin barrier defects in healthy human volunteers were investigated.

The experimental studies point towards new molecular insights into AHR’s function in skin biology and underscore the potential of AHR ligands as a therapeutic modality in the treatment of inflammatory skin diseases.