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

ABSTRACT: 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-?. Adoptively transferring CD83+ CCR7+ NK cells aggravates EAU symptoms and increases the number of CD4+ IFN-?+ T cells and dendritic cells (DCs) within the eye. These CD83+ CCR7+ NK cells then promote the maturation of DCs and IFN-? 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.

SUBMITTER: Fu Q 

PROVIDER: S-EPMC6378215 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature