Open AccessCD83 + CCR7 + NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis
Author(s) -
Fu Qiang,
Man Xuejing,
Wang Xin,
Song Nannan,
Li Yuanbin,
Xue Jiangnan,
Sun Yufei,
Lin Wei
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14081
Subject(s) - c c chemokine receptor type 7 , interleukin 12 , immunology , interleukin 21 , antibody , janus kinase 3 , biology , cytotoxic t cell , t cell , immune system , in vitro , chemokine , chemokine receptor , biochemistry
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.