CD83+CCR7+ NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis

摘要

Natural killer (NK) cells have been reported to play a pathological role in autoimmune uveitis. However, the mechanisms regarding NK cells in uveitis and factors that affect NK‐cell activation in this condition remain unclear. Here, we report that the number of CD3sup‐/supNK1.1sup+/supCD83sup+/supCCR7sup+/sup cells is increased in the inflamed eyes within a mouse model of experimental autoimmune uveitis (EAU), and these cells express elevated levels of NKG2D, CD69 and IFN‐γ. Adoptively transferring CD83sup+/supCCR7sup+/supNK cells aggravates EAU symptoms and increases the number of CD4sup+/supIFN‐γsup+/supT cells and dendritic cells (DCs) within the eye. These CD83sup+/supCCR7sup+/supNK cells then promote the maturation of DCs and IFN‐γ expression within T cells as demonstrated in vitro. Furthermore, IL‐18, as primarily secreted by DCs in the eyes, is detected to induce CD83sup+/supCCR7sup+/supNK cells. In EAU mice, anti‐IL‐18R antibody treatment also decreases retinal tissue damage, as well as the number of infiltrating CD83sup+/supCCR7sup+/supNK cells, T cells and DCs in the inflamed eyes and spleens of EAU mice. These results suggest that CD83sup+/supCCR7sup+/supNK cells, as induced by IL‐18 that primarily secreted by DCs, play a critical pathological role in EAU. Anti‐IL‐18R antibody might serve as a potential therapeutic agent for uveitis through its capacity to inhibit CD83sup+/supCCR7sup+/supNK cells infiltration.