237 Impact of innate immunity on pemphigus vulgaris disease manifestation

Pemphigus vulgaris is a chronic autoimmune blistering disease characterized by antibody production against Desmogleins 3 (Dsg3) and 1 (Dsg1) causing acantholysis. Increased levels of innate cytokines detected in the blister fluid suggest role immune system activity. To elucidate discrepancy between binding pathogenic antibodies lack formation, we focused on cofactors supporting Here, used dispase-based keratinocyte-dissociation assay with human immortalized keratinocyte cell line (HaCaT) primary keratinocytes. Besides fragmentation, induction was RT-PCR ELISA. transfer these vitro conditions to more physiological setting, performed studies ex vivo skin explants. We were able identify factors inducing (UVA, bacterial toxins, Poly I:C) which enhance acantholysis induced anti-Dsg3 AK23. Ex vivo, observed synergistic effect AK23 (subpathogenic level) UVA (non-toxic intensity). The augmented as well cytokine release seem be caspase-dependent effects reversible (pan-)caspase inhibitors. Interestingly, recombinant IL-1 itself did not increase fragmentation vitro, adding hypothesis that but rather an up-stream signaling event could pathogenetically relevant. Our findings lead us conclusion activation might favor autoantibody formation. execution depends caspase most probably inflammasome activation. molecular components pathways possible therapeutic targets management.