Abstract
<jats:p>The skin barrier protects the body against water loss, harmful substances, and pathogens. In atopic dermatitis, this barrier is impaired, but the underlying mechanisms are not yet fully understood. This thesis combines molecular, biophysical, and bioinformatic approaches to investigate the regulation of the skin barrier in an interdisciplinary approach. It demonstrates that the aryl hydrocarbon receptor (AHR) regulates the maturation of skin cells through the transcription factor TFAP2A and through TFAP2A promotes the formation of a healthy skin barrier. In addition, it shows that electrical impedance spectroscopy is a suitable, non-invasive method for objectively measuring barrier function in cultured human epidermis models. This enhances the scientific relevance and applicability of animal-free skin models. Finally, the analysis of individual skin cells from patients with atopic dermatitis reveals that the disease is associated with an expansion of a stem cell-like keratinocyte population characterized by altered differentiation and potentially pro-inflammatory programs. This finding challenges the classical model, in which epidermal hyperproliferation is primarily attributed to an increased number of transit-amplifying cells. Together, these findings deepen our understanding of skin barrier biology and contribute to the broader application of animal-free skin models, the development of more objective methods for assessing barrier function, and the identification of new therapeutic targets for atopic dermatitis.</jats:p>