Conjunctiva Resident gamma delta T Cells Expressed High Level of IL-17A and Promoted the Severity of Dry Eye

PURPOSE. Conjunctival inflammation promotes ocular surface disorders in dry eye disease (DED). Here we identified gamma 8 T cells as the predominant source of IL-17A in the murine conjunctiva and assessed their contribution to the pathogenesis of DED. METHODS. We enrolled 22 patients with DED, and analyzed the proportion of gamma 8 T cells in the conjunctival epithelial samples by flow cytometry. Adult C57Bl/6 wild-type and TCR8-/- mice were used to induce DED models to investigate the role of gamma 8 T cells. The characteristics of immune cell infiltration and the expression of immune-related cytokines or markers in mouse conjunctiva were analyzed by flow cytometry, Western blot, and quantitative polymerase chain reaction. RESULTS. The proportion of gamma 8 T cells in the human DED conjunctiva is significantly higher in patients with severe corneal epithelial defects than in mild ones, which is consistently observed in the murine DED model. Further, a high level of IL-17A but not IFN-gamma is detected in the conjunctiva of mice. The increased murine IL-17A-producing cells on the conjunctiva are identified as gamma 8 T cells predominantly and Th17 cells to a lesser extent. Ablation of gamma 8 T cells by antibody depletion or genetic deletion of TCR8 alleviates ocular surface damage in the murine DED model. CONCLUSIONS. Our studies evaluate human and experimental murine DED for evidence of gamma 8 T-cell-mediated inflammation and highlight a potential therapeutic synergy by targeting IL-17 and gamma 8 T cells in DED treatment.