Complement C3 as key driver of pemphigoid disease pathogenesis

Pemphigoid diseases (PD) are characterized by autoantibodies targeting structural proteins of the dermal-epidermal junction zone (DEJ). Local skin deposition of the third component of the complement cascade (C3) is regularly used as clinical marker in the diagnosis of PDs.Locally C3 and its activation products perpetuate and aggravate inflammation, while also contributing to tissue homeostasis through opsonization of cell debris. Systemically the interaction of the downstream C3 activation product C3d and its receptor CR2 augments and drastically enhances the humoral immune response towards antigens. The implication of this systemic role of C3(d) in the development of autoantibodies and thus autoimmune disease has not yet been addressed. By using wildtype (wt) and C3 knockout (C3KO) mice in an experimental model of active, immunization induced epidermolysis bullosa acquisita (EBA), a prototypic PD, we aim to gain insights into both systemic and local effects of C3 in this model system.