Role of dendritic cells in immunopathogenesis of Pemphigus vulgarism (BA7P.149)

Abstract Pemphigus vulgaris (PV) is an autoimmune blistering disease that affects skin and mucous membranes characterized by autoantibodies against Dsg3. The breach in immune tolerance, aberrant T cell function and antigen presentation are key immunological events in autoimmunity. Given the central role in induction of immune response and tolerance, dendritic cells (DCs) are most important cells in inciting and sustaining autoimmunity, but it has not yet been explored in PV. We have previously identified potential role of Th cells in pathogenesis of PV. In this study, DC frequency was estimated using HLA-DR, Lin1, CD11c and CD123 by flowcytometry. A significant decline in mDC & pDC frequency in circulation of PV patients (n=20) vs. controls (n=15) was observed. Further, molecular functional characteristics were assessed in cultured monocyte derived differentiated DCs and sorted DCs (FACS AriaIII) directly from circulation of patients and controls. The mRNA levels of their co-stimulatory molecules were estimated. Expression levels of stimulatory molecules (CD40 & CD80) was found to be significantly increased, while a significant decline in inhibitory markers (PSGL1 & ILT3) was observed in sorted and cultured DCs from patients vs. controls. Increased expression level of stimulatory molecules and decreased level of inhibitory molecules further strengthens the defect in functional status of DC. Thus, these co-stimulatory molecules might be a promising avenue for novel therapeutics in PV.