Pemphigoid diseases (PDs) are a group of well-defined autoimmune blistering diseases (AIBDs) that are caused by autoantibodies against structural proteins of the dermal-epidermal junction (DEJ) resulting in the characteristic formation of skin blisters and erosins.
The autoantibodies induce an inflammatory cascade eventually resulting in the generation o f the anaphylatoxin C5a, which recruits and activates neutrophils. Such neutrophils secrete proteolytic enzymes and reactive oxygen species (ROS), which induce a separation of the epidermis from the dermis.

While we could demonstrate that C5a receptor 1 (C5aR1) deficiency protects from skin blistering in a passive model of epidermolysis bullosa acquisita (EBA) (Karsten et al. Nat Med 2012), the role of C5aR2 in AIBDs had not been addressed. We have therefore recently examined C5aR2-deficient mice in a passive bullous pemphigoid (BP) mouse model. Deficiency in C5aR2 significantly aggravated skin inflammation, indicating a protective role of this receptor in the effector phase of PDs (Karsten et al. Front Immunol 2018). The mechanisms of this protective role of C5aR2 in AIBD are still unknown. Likewise, it is still elusive whether the protective effects mediated via C5aR2 can be harnessed for therapeutic purposes. In this project, we aim to elucidate the role of C5aR2 in the regulation of AIBD-driven skin inflammation and its potential as therapeutic target in the treatment of AIBDs.