This research project explores the use of three-dimensional skin equivalents (3DSE) as an innovative human-based model to study pemphigoid diseases (PD). These chronic autoimmune blistering disorders, such as bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA), are driven by autoantibodies against structural proteins of the dermal–epidermal junction, causing inflammation, tissue damage, and blister formation. Compared to conventional animal or 2D models, three-dimensional skin equivalents (3DSE) provide an anatomically and immunologically relevant platform that closely mimics the complexity of human skin. In addition, they enable the evaluation of therapeutic candidates, such as Fc receptor blockers or complement inhibitors, in a preclinical human setting.
Within this project, 3DSE generated from keratinocytes and fibroblasts will be optimized to investigate disease-relevant mechanisms. Autoantibodies against BP180, p200, and COL7, along with their subclasses and glycoforms, will be analyzed for their pathogenic potential. In addition, the contribution of innate immune cells like neutrophils and eosinophils to dermal–epidermal separation will be studied. Readouts such as histology, immunofluorescence, and ELISA will provide detailed insights into complement activation and inflammatory pathways.
Ultimately, the establishment of this model aims to deepen the understanding of PD pathogenesis, reduce reliance on animal experimentation in accordance with the 3Rs principle, and create a foundation for testing future therapeutic strategies in a clinically relevant setting