Contact lens-induced corneal parainflammation involving Ly6G+cell infiltration requires IL-17A and 8 T cells

Purpose: Previously, using a murine model, we reported that contact lens (CL) wear induced corneal para-inflammation involving CD11c+ cells after 24 h and Ly6G+ cells (neutrophils) after 5-6 days. Here, we inves-tigated the role of IL-17 and gamma 8 T cells in the CL-induced neutrophil response.Methods: CL-wearing C57BL/6 wild-type (WT) mice were compared to lens-wearing IL-17A/F single or double gene knock-out mice, or mice treated with UC7-13D5 monoclonal antibody to functionally deplete gamma 8 T cells. Contralateral eyes served as no lens wear controls. Corneal Ly6G+ and gamma 8 T cell responses were quantified as was expression of genes encoding pro-inflammatory cytokines IL-17A/F, IL-(i, IL-18 and expression of IL-17A/F protein.Results: After 6 days lens wear, WT corneas showed Ly6G+ cell infiltration while remaining free of visible pa-thology. In contrast, lens-wearing corneas of IL-17AF (-/-), IL-17A (-/-) mice and gamma 8 T cell-depleted mice showed little or no Ly6G+ cell infiltration. No Ly6G+ cell infiltration was detected in contralateral eye controls. Lens-wearing WT corneas also showed a significant increase in gamma 8 T cells after 24 h that was maintained after 6 days of wear, and significantly increased cytokine gene expression after 6 days versus contralateral controls: IL-18 & IL-17A (-3.9 fold) and IL-23 (-6.5-fold). Increased IL-17A protein (-4-fold) was detected after 6 days lens wear. gamma 8 T cell-depletion abrogated these lens-induced changes in cytokine gene and protein expression.Conclusion: Together, these data show that IL-17A and gamma 8 T cells are required for Ly6G+ cell (neutrophil) infiltration of the cornea during contact lens-induced parainflammation.