030 The Role of FasL-dependent Signaling in the Pathogenesis of Pemphigus Vulgaris

Pemphigus vulgaris is a chronic, life-altering bullous autoimmune disease with production of antibodies against the desmosomal proteins Desmogleins 3 and 1 (Dsg) causing acantholysis. Ubiquitous antibody deposition but discontinuous manifestation indicate possible role cofactors. In this study, we focus on FasL as putative cofactor in PV-related To study cell-death dependent processes during PV, used spontaneously immortalized keratinocyte cell line HaCaT stimulated AK23 (anti-Dsg3 ab) together cofactor. aim 1. tested stability monolayers dispase-based keratinocyte-dissociation assay, 2. studied cleavage status various by Western Blot 3. investigated viability death via Crystal Violet FACS. an activator extrinsic apoptotic pathway. our experiments, first defined sublethal concentration that was sufficient to activate caspase cascade did not yet lead acantholysis vitro. Costimulation resulted increased fragmentation compared stimulation alone. Importantly, treatment alone for 4h led partial 8 (initiator caspase), while following activated. Even after prolonged incubation AK23, there no increase death. these results, pan-caspase inhibitor zVAD-fmk could prevent from AK23-induced This further confirmed cells overexpressing cFLIP short which activation blocked. These data suggest although relevant early acantholytic processes, cascade-inducing cofactors may have impact pathogenesis pemphigus vulgaris. great interest due interactions inflammatory caspases other signaling pathways context pathophysiology therapeutic approaches.