Project 4: “Bullous pemphigoid – What makes the blister?”
Prof. Ulrike Raap
Department of Dermatology and Allergy
University Hospital, Klinikum Oldenburg AöR
Faculty of Medicine and Health Sciences
University of Oldenburg
Prof. Marcel F. Jonkman
Center for Blistering Diseases
Department of Dermatology
University of Groningen
University Medical Center Groningen
Summary: Bullous Pemphigoid (BP) is one of the most common autoimmune diseases of the skin for which there is currently no cure. Early symptoms include urticarial erythema and severe itch, with tense blisters that occur in later stages of classical BP. Interestingly, there is a subgroup of patients without blisters which display erythematous-urticarial plaques as well as severe itch. The latter is known as non-bullous cutaneous pemphigoid; it is not readily diagnosed and the pathophysiology is poorly understood. Classical BP is characterized by a substantial accumulation of eosinophils in subepidermal blisters, skin lesions as well as blood eosinophilia. Additionally, skin lesions of classical BP contain increased numbers of basophils. In this study we aim to identify potential effector functions of eosinophil and basophil granulocytes in BP to discover what drives blister formation and the immunological differences between non-bullous and bullous cutaneous pemphigoid. We will focus on skin sections to investigate the accumulation, activation and signaling processes of eosinophil and basophil granulocytes to elucidate the mechanisms that regulate bullous and nonbullous cutaneous pemphigoid. Cytokine profiling and RNA sequencing will elucidate the complex mechanisms that govern the inflammatory processes in BP. In addition, transcriptome analysis and proteomic studies will unravel signaling pathways which regulate the activation of basophils and eosinophils. Finally, we will establish an ex vivo skin model for BP to reveal whether basophils drive the inflammation associated with BP. We hypothesize that basophils potentially play an important role in inducing the chemotaxis of eosinophils and their functional activation and thereby facilitate the development of blisters in BP. Our study will help us to understand the differential functional roles of eosinophils and basophils in bullous and non-bullous cutaneous pemphigoid in order to establish novel therapeutic treatment strategies against this debilitating disease of the elderly.
Specific requirements for PhD candidates for project 4: Master (or equivalent) of Biomedical Technology, Medical Biology, Medicine or Pharmacology.