IFN-γ-Expressing Th17 Cells Are Required for Development of Severe Ocular Surface Autoimmunity

Th17 cells are critical effectors mediating the ocular surface autoimmunity in dry eye disease (DED). Increased IFN-gamma has also been implicated in DED; however, it remains unclear to what extent Th1 cells contribute to DED pathogenesis. In this study, we investigated the cellular source of IFN-gamma and assessed its contribution to corneal epitheliopathy in DED mice. We discovered a significant IL-17A(+) IFN-gamma(+) (Th17/1) population and determined that these cells are derived from Th17 precursors. Adoptive transfer of Th17/1, but not Th1, cells confers the disease to naive recipients as effectively as do Th17 cells alone. DED-induced IL-12 and IL-23 are required for in vivo transition of pathogenic Th17 cells to IFN-gamma producers. Furthermore, using IFN-gamma-deficient Th17 cells, we demonstrate the disease-amplifying role of Th17-derived IFN-gamma in DED pathogenesis. These results clearly demonstrate that Th17 cells mediate ocular surface autoimmunity through both IL-17A and IFN-gamma.