This thesis explores disease mechanisms in atopic dermatitis (AD), focusing on epidermal barrier function, immune responses, and host-microbiome interactions. Using advanced 3D organotypic human epidermal equivalent (HEE) models with primary and N/TERT keratinocytes, the work investigates cytokine-driven hyperproliferation, barrier defects, and microbial dysbiosis in AD. A key focus is on the aryl hydrocarbon receptor (AHR) pathway, a promising therapeutic target that modulates keratinocyte differentiation, barrier integrity, antimicrobial peptide production, and microbiome composition. The thesis highlights the potential of novel AHR ligands and established therapies like coal tar. Innovative models were developed to study microbial interactions, revealing that commensal Gram-positive anaerobic cocci (GPAC) can activate immune responses and may help limit Staphylococcus aureus colonization via AHR signaling. The findings support targeting epidermal homeostasis and AHR pathways for AD treatment and provide valuable tools for translational dermatology research and drug development.
Gijs Rikken (1986, Groesbeek) obtained an MSc in Natural Sciences from Radboud University and conducted PhD research in Experimental Dermatology at Radboudumc, specializing in molecular, cellular, and microbiology. He is currently employed as a technology specialist in the food sector and will be available for new academic or research-oriented opportunities from August 2025.