Comprehending the phenotypic and functional diversity of γδ T cell subtypes in autoimmune skin disease Pemphigus Vulgaris

Abstract

Abstract Pemphigus vulgaris (PV) is an atypical form of mucocutaneous autoimmune disease caused due to the formation of auto-antibodies against desmoglein3 (Dsg3) and anomalous T cell function. Gamma Delta T cells (γδ T cells) are evolutionary conserved distinctive cells that maintain the immune surveillance at the epithelial surface. The role of γδ T cells and their plasticity is not yet illustrated in the immunopathogenesis of PV. γδ T cells isolated from the PV patients showed diverse phenotypes (γδ1, γδ2, γδ17, γδreg) and functionality, such as migration, and multiple cytokine productions. Significantly higher frequency of γδ T cells producing IFN-γ & IL-17 (8.5% vs. 5.2%) was found in the circulation PV patients compared to control. Circulation of PV patients indicated higher number of CCR6+ γδ T cells suggesting their migratory potential. Cytotoxic activity of γδ T cells from PV patients (30±8%) was observed to be higher as compared to control (16±5%). Primary culture of γδ T cells from PV patients showed increased mRNA expression of inflammatory cytokines (IL17, ROR γt, IL-23) and co-stimulatory markers (CD27 and CD70). The regulatory markers associated with regulatory γδ T cells (TGFβ, FoxP3) were downregulated. At the tissue level, γδ 17 T cells in patient skin showed increased IL-17, CCR6 expression while CCR4 receptor associated with γδ reg T cells has shown lower expression indicating their imbalance and possible involvement in the immunopathogenesis of PV. These maiden findings suggest the versatile nature of γδ T cells that will help to find a better approach for novel therapeutics for PV.