Retinal Astrocytes respond to IL-17 differently than Retinal Pigment Epithelial cells

IL-17+ T cells make up the majority of the infiltrating cells in the inflamed eye during the development of EAU. However, the role of IL-17 in ocular inflammation is poorly defined. Given that the primary target cells for IL-17 are parenchymal cells of the tissue, we investigated the in vitro effect of IL-17 on mouse RACs and RPE cells. Our results showed that although RACs and RPE cells expressed the IL-17R, RACs responded to IL-17 by producing increased amounts of proinflammatory cytokines and chemokines, leading to increased migration of granulocytes, whereas RPE cells responded to the same concentration of IL-17 by expressing increased levels of SOCS proteins, resulting in only limited production of proinflammatory cytokines and chemokines and an increased amount of suppressive cytokines, such as LIF. The combination of IL-17 and IFN-gamma had a synergistic effect on cell migration with RACs but an antagonistic effect with RPE. In addition, specific inhibitors of the PI3K/Akt signaling pathway completely blocked inflammatory cell migration induced by chemokines released by IL-17-stimulated RACs. Our results demonstrate that IL-17 can induce a pro- or anti-inflammatory effect in the eye, depending on the parenchymal cells stimulated.