Notch信号通路调控CD4^+T细胞分泌IL-22在Vogt-小柳原田综合征中的作用  

Notch signaling pathway regulates IL-22 secretion by CD4^+T cells in patients with Vogt-Koyanagi-Harada syndrome

作　　者：储昭节 王彤[1] 马强[1] 范晶晶 蔡敏 Zhao-Jie Chu;Tong Wang;Qiang Ma;Jing-Jing Fan;Min Cai(Department of Ophthalmology, Xi’an First Hospital, Xi’an Eye Hospital, Eye Institute of Shaanxi Province, Xi’an 710002, Shaanxi Province, China)

机构地区：[1]中国陕西省西安市第一医院眼科西安市眼科医院陕西省眼科研究所

出　　处：《国际眼科杂志》2019年第7期1114-1118,共5页International Eye Science

摘　　要：目的:观察Notch受体和IL-22在Vogt-小柳原田(VKH)综合征患者中的表达变化,探讨Notch信号通路对VKH综合征患者CD4^+ T细胞分泌IL-22的调控作用。方法:选取VKH综合征患者35例(活动期15例和静止期20例)和健康对照者12例,分选血浆和CD4^+ T细胞, qRT-PCR和Western blot法检测Notch受体,ELISA法检测血浆IL-22表达,流式细胞术检测Th17和Th22的比例。观察抑制Notch信号通路对VKH综合征患者CD4^+ T细胞转录因子相对表达量和IL-22分泌水平的变化。结果:活动期VKH综合征患者CD4^+ T细胞中Notch1~3较静止期和健康对照者显著升高。活动期VKH综合征患者血浆IL-22及Th17、Th22水平高于静止期和健康对照者。抑制Notch信号通路可导致活动性VKH综合征患者CD4^+ T 细胞中AhR mRNA降低,分泌IL-22水平降低。结论:Notch-AhR-IL-22信号通路可能参与了VKH综合征的发病。AIM:To investigate the changes of Notch receptors and interleukin (IL)-22 expression in patients with Vogt-Koyanagi-Harada (VKH) syndrome, and to assess the regulatory activity of Notch signaling to IL-22 production by CD4^+ T cells in patients with VKH syndrome. METHODS: Thirty-five patients with VKH syndrome (including fifteen active VKH and twenty inactive VKH) and twelve healthy controls were enrolled. Plasma was isolated, and CD4^+ T cells were purified. Notch receptors were investigated by qRT-PCR and Western blot. Plasma IL-22 expression was measured by ELISA. The percentage of Th17 and Th22 cells was investigated by flow cytometry. CD4^+ T cells, which were purified from active VKH patients, were stimulated with Notch signaling inhibitor DAPT. mRNA expression of transcription factor in CD4^+ T cells as well as IL-22 secretion by CD4^+ T cells was investigated. RESULTS: Notch1-Notch3 in CD4^+ T cells from active VKH syndrome patients was significantly elevated in comparison with inactive VKH and healthy controls. Plasma IL-22 expression and percentage of Th17 and Th22 was notably increased in active VKH syndrome in comparison with inactive VKH and controls. DAPT stimulation inhibited Notch signaling pathway in CD4^+ T cells, leading to the down-regulation of AhR mRNA and IL-22 secretion. CONCLUSION:Notch-AhR-IL-22 signaling pathway might take part in the pathogenesis of VKH syndrome.

关 键 词：VOGT-小柳原田综合征 Notch信号通路 白细胞介素-22 CD4^+T淋巴细胞 

分 类 号：R773.9[医药卫生—眼科]