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

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 CD3^- NK1.1⁺ CD83⁺ CCR7⁺ 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 CD83⁺ CCR7⁺ NK cells aggravates EAU symptoms and increases the number of CD4⁺ IFN-γ⁺ T cells and dendritic cells (DCs) within the eye. These CD83⁺ CCR7⁺ NK 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 CD83⁺ CCR7⁺ NK cells. In EAU mice, anti-IL-18R antibody treatment also decreases retinal tissue damage, as well as the number of infiltrating CD83⁺ CCR7⁺ NK cells, T cells and DCs in the inflamed eyes and spleens of EAU mice. These results suggest that CD83⁺ CCR7⁺ NK 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 CD83⁺ CCR7⁺ NK cells infiltration.