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‐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.

Signature of Circulating Biomarkers in Recurrent Non-Infectious Anterior Uveitis. Immunomodulatory Effects of DHA-Triglyceride. A Pilot Study

“…However, in our recurrent NIAU cohort, we also detected significantly increased plasma levels of IL-10 (an important inhibitor of the production of proinflammatory cytokines, such as IL-1β and IL-6). The cytokines that we detected in the plasma of the study participants was significantly increased in the recurrent NIAU patients in its inactive stage, and several of these cytokines mainly appear in relation to natural killer (NK) cells, such as IL-6, which plays an important role in NK cells activation, or IL-10, which can be released from activated NK cells, as previously reported [60,61]. Furthermore, it has been shown that CD4 and CD8 T cell surface molecules are essential for the recognition and activation of T cells by binding to their corresponding class II/class I major histocompatibility complex ligands on an antigen-presenting cell.…”

“…Furthermore, it has been shown that CD4 and CD8 T cell surface molecules are essential for the recognition and activation of T cells by binding to their corresponding class II/class I major histocompatibility complex ligands on an antigen-presenting cell. In fact, CD4 and CD8 can increase the antigen-induced IL-2 formation through distinct mechanisms [ 60 , 61 , 62 , 63 ]. Additionally, CD4+ T cells can promote NK cells and macrophages via INFγ, to kill host cells in certain conditions.…”

Molecular, Cellular and Functional Changes in the Retinas of Young Adult Mice Lacking the Voltage-Gated K+ Channel Subunits Kv8.2 and K2.1

“…NK cells are a central component of the innate immune system and play a critical role in regulating the adaptive immune response. Those cells are known to have an essential role in generating the inflammatory response during uveitis [ 33 , 34 ] and in AMD pathogenesis [ 35 ].…”

Dracocephalum heterophyllum (DH) Exhibits Potent Anti-Proliferative Effects on Autoreactive CD4+ T Cells and Ameliorates the Development of Experimental Autoimmune Uveitis

“…6- to 8-week-old C57BL/6 mice were anesthetized by intraperitoneal injection of pentobarbital sodium (80 mg/kg). EAU was induced by active immunization as previously described ( 17 ). Briefly, mice were immunized with 400 μg inter-photoreceptor retinoid-binding protein (IRBP)1-20 (5 mg/ml, GPTHLFQPSLVLDMAKVLLD, purchased from China Peptides) emulsified 1:1 in complete Freund’s adjuvant (Chondrex) with an additional 100 μl mycobacterium tuberculosis H37R (5 mg/ml, BD biosciences) at six locations (footpads (2×), tail base, posterior neck and bilateral flanks (2×)).…”