MD A1: Investigation of the influence of specific CDK inhibitors on neutrophil activation

Pemphigoid diseases (PDs) are a group of autoimmune diseases caused by an autoantibody-mediated immune response against certain components of the hemidesmosomal anchoring complex at the dermal-epidermal junction (DEJ) of the skin and mucous membranes. The common clinical-histological correlate are subepidermal blisters, which later develop into erosions and crusts on the skin and / or mucous membranes. All PDs have a chronic and often therapy-refractory course.Treatment strategies for PDs rely almost exclusively on systemic immunosuppression, especially high-dose corticosteroids. However, iatrogenic immunosuppression contributes significantly to increased mortality. Due to the inadequate treatment options and the increasing incidence of PD, effective and safe therapeutic strategies for patients with PD are urgently needed.The activation of neutrophils causes the release of reactive oxygen species (ROS) and proteolytic enzymes, which ultimately lead toblistering and the clinical picture of PDs.In the context of the present project, we would like to investigate the effect of cyclin-dependent kinases inhibitors with the potential to influence neutrophil activation. This is the prerequisite for a later application of these kinase inhibitors in animal models and also with a view to an application in patients with PDs and other IC-induced autoimmune diseases.