Dominance and improved survivability of human æT17 cell subset aggravates the immunopathogenesis of pemphigus vulgaris

Human gamma delta T cells are highly enriched in epithelial cell-dominated compartments like skin. Nonetheless, their function in the pathogenesis of pemphigus vulgaris (PV), an autoimmune skin disorder, is lacking. Therefore, we investigated the functional expression of human gamma delta T cell subsets along with their homing chemokine receptor-ligand and inflammatory cytokines in the immunopathogenesis of PV. Estimation of the frequency of gamma delta T cell subsets by flow cytometry revealed four major subsets of gamma delta T cells (gamma delta T1,gamma delta T2,gamma delta T17,gamma delta Treg) in both control and PV circulation. The elevated frequency of gamma delta T17 cells producing IL17 and expressing CCR6 receptor suggests their inflammatory and migratory potential in PV. In vitro culture of gamma delta T cells from patients showed increased mRNA expression of inflammatory cytokines IL17, ROR gamma t, IL23, IL1, and co-stimulatory markers, CD27 and CD70. These findings correlated the role of IL1 and IL23 cytokines that alleviate the Th17 population in PV. Cytotoxic activities of gamma delta T cells were higher and inflammatory gamma delta T17 cells were localized in the skin of PV whereas gamma delta Treg cells associated TGF beta and FOXP3 were lowered. Hyperinflammatory phenotype of the gamma delta T17 cell subset and its migratory potential might be aiding in the pathogenesis of PV, whereas gamma delta Treg cells fail to suppress these inflammatory responses. Hence,.dT17 cell-associated markers can be targeted for identifying novel therapeutics in PV.