Kinase cascades in neutrophils as therapeutic target in pemphigoid disease

Pemphigoid diseases (PD) are a group of autoimmune bullous skin diseases which are characterised by the activation of neutrophils resulting in reactive oxygen species- and protease-mediated tissue damage. Clinically, patients suffer from skin blisters and erosions. The effector functions are triggered by binding of immunoglobulin gamma autoantibodies deposited at the dermal-epidermal junction to fragment crystallisable gamma receptors (FcγR) on neutrophils subsequently activating kinase signalling cascades. Therefore, the kinases downstream of FcγRs are promising therapeutic targets in PDs. However, the signalling pathways are only poorly understood, raising the need for further investigation. This project aims to comprehensively characterise the kinase cascades downstream of FcγR activation in neutrophils in both human and murine context and to examine the effect of inhibiting select kinases for therapeutic purposes in PDs.