IFN-{gamma}-Expressing Th17 Cells Are Required for Development of Severe Ocular Surface Autoimmunity [MUCOSAL IMMUNOLOGY]

Th17 cells are critical effectors mediating the ocular surface autoimmunity in dry eye disease (DED). Increased IFN- 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- and assessed its contribution to corneal epitheliopathy in DED mice. We discovered a significant IL-17A⁺IFN-⁺ (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- producers. Furthermore, using IFN-–deficient Th17 cells, we demonstrate the disease-amplifying role of Th17-derived IFN- in DED pathogenesis. These results clearly demonstrate that Th17 cells mediate ocular surface autoimmunity through both IL-17A and IFN-.

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