The role of aryl hydrocarbon receptor in uveitis and the mechanism

HUANG Yike; DONG Jia; DAI Qinjin; DUAN Honglin; WANG Xixi; WU Juan; YANG Peizeng; HOU Shengping

doi:10.13431/j.cnki.immunol.j.20180078

Abstract：Uveitis is characterized as a common cause of blindness. Aryl hydrocarbon receptor (Ah R) has been implicated in immunomodulatory processe in human uveitis, although the exact mechanisms remain poorly understood. This study aimed to explore the role of a Ah R ligand 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in experimental autoimmune uveitis (EAU) and related mechanism. Female C57 BL/6 mice were randomly divided into three groups: na(i)ve group, EAU + vehicle group, and EAU + TCDD group. Mice were immunized with interphotoreceptor retinoid-binding protein 651-670 (IRBP651-670) to induce experimental autoimmune uveitis. TCDD was administered intraperitoneally one day before immunization in EAU + TCDD group, while the equal volume of vehicle (olive oil) was administered in the same way to the EAU+vehicle group. The severity of EAU was evaluated with clinical and histological scores. We also tested the number of macrophage/microglia and the production pro-inflammatory cytokines. Data showed that clinical and histopathological manifestations were significantly ameliorated in the EAU+TCDD group as compared with the EAU+vehicle group. In addition, TCDD decreased the number of F4/80 positive macrophage/microglia, inhibited the expressions of pro-inflammatory cytokines, and reduced the activation of Notch-1. In conclusion, Ah R activation with TCDD exhibits an anti-inflammatory effect by reducing the number of macrophages/microglia, decreasing pro-inflammatory cytokines, and inhibiting the Notch pathway during EAU.