摘要目的:初步探讨白细胞介素（IL）-23受体（IL-23R）过表达对实验性自身免疫性葡萄膜炎（EAU）模型小鼠辅助性T细胞17 （Th17细胞）/调节性T细胞（Treg细胞）平衡的影响。方法:8周龄雌性C57BL/6J小鼠12只，随机分为LV-Ctrl组、LV-IL-23R组，每组各6只。两组小鼠经尾静脉分别注射LV-Ctrl、LV-IL-23R慢病毒；注射后7 d采用光感受器间维生素A类结合蛋白 1-20主动免疫构建EAU小鼠模型。免疫后13 d开始，每2天使用间接检眼镜观察小鼠眼底并进行临床评分。免疫后30 d，苏木精-伊红染色观察小鼠视网膜组织病理学改变。酶联免疫吸附测定检测两组小鼠血清中IL-17水平；流式细胞仪检测Th17细胞和Treg细胞比例；实时荧光定量聚合酶链反应检测IL-23R、IL-17、维甲酸相关孤儿受体γt （RORγt）、IL-10和叉头状转录因子p3 (Foxp3） mRNA相对表达量。组间比较采用重复测量方差分析、独立样本Mann-Whitney U检验和独立样本 t检验。 结果:与LV-Ctrl组比较，LV-IL-23R组小鼠视网膜炎症反应更重。免疫后13 d，LV-IL-23R组、LV-Ctrl组小鼠眼底炎症评分差异无统计学意义（ t=-2.001， P=0.058 ）；免疫后15~ 29 d，LV-IL-23R组小鼠眼底炎症评分均高于LV-Ctrl组，差异有统计学意义（ t=-4.429、-6.578、-7.768、-10.183、-6.325、-7.304、-4.841、-6.872， P<0.001）。组织病理学检查显示，与LV-Ctrl组比较，LV-IL-23R组眼底炎性细胞浸润增多，视网膜结构破坏更为严重，组织病理学评分显著升高，差异有统计学意义（ t=-4.339， P=0.001）。与LV-Ctrl组比较、LV-IL-23R组小鼠脾脏中IL-23R mRNA相对表达量显著升高，差异有统计学意义（ Z=2.087， P=0.037）；T细胞中IL-17、RORγt mRNA相对表达量增加，IL-10、Foxp3 mRNA相对表达量降低，差异均有统计学意义（ t=-6.313、-5.922、4.844、7.572， P=0.003、0.004、0.008、0.002 ）。与LV-Ctrl组比较、LV-IL-23R组小鼠血清中IL-17水平明显升高，差异有统计学意义（ t=-5.423 ， P=0.002）；脾脏和淋巴结中Th17细胞比例明显升高，Treg细胞比例显著降低，差异有统计学意义（ t=-4.290、3.700， P=0.002、0.006）。 结论:IL-23R过表达可促使EAU小鼠的Th17/Treg失衡，加重EAU临床及病理表现。

abstractsObjective:To investigate the effect of interleukin (IL)-23 receptor (IL-23R) overexpression on the balance of T helper 17 (Th17 cells)/regulatory T cells (Treg cells) in experimental autoimmune uveitis (EAU) mice.Methods:Twelve 8-week-old female C57BL/6J mice were randomly divided into LV-Ctrl group and LV-IL-23R group, with 6 mice in each group. Two groups of mice were injected with LV-Ctrl and LV-IL-23R lentiviruses through the tail vein, respectively; 7 days after injection, the EAU mouse model was established by active immunization with vitamin A-binding protein 1-20 between photoreceptors. Starting from 13 days after immunization, the fundus of the mice was observed by indirect ophthalmoscopy every 2 days and clinical scores were performed; 30 days after immunization, hematoxylin-eosin staining was used to observe the histopathological changes of mouse retina. The levels of IL-17 in serum of the two groups of mice were detected by enzyme-linked immunosorbent assay; the proportion of Th17 cells and Treg cells was detected by flow cytometry. The relative mRNA expression of IL-23R, IL-17, retinoic acid-related orphan receptor γt (RORγt), IL-10 and forkhead transcripyion factor p3 (Foxp3) were detected by real-time quantitative polymerase chain reaction. Comparisons between groups were performed using repeated measures analysis of variance, independent samples Mann-Whitney U test, and independent samples t test. Results:Compared with the LV-Ctrl group, the retinal inflammatory reaction of the LV-IL-23R group was more severe. At 13 days after immunization, there was no significant difference in fundus inflammation scores between LV-IL-23R group and LV-Ctrl group ( t=-2.001, P=0.058); 15-29 days after immunization. The fundus inflammation scores of LV-IL-23R group were higher than those of LV-Ctrl group, and the difference was statistically significant ( t=-4.429,-6.578, -7.768, -10.183, -6.325, -7.304, -4.841, -6.872; P<0.001). Histopathological examination showed that the infiltration of inflammatory cells in the fundus increased, the retinal structure was damaged more seriously, and the histopathological score was significantly increased, and the difference was statistically significant ( t=-4.339, P=0.001). Compared with the LV-Ctrl group, the relative expression of IL-23R mRNA in the spleen of the LV-IL-23R group was significantly increased, and the difference was statistically significant ( Z=2.087, P=0.037). The relative expression of IL-17 and RORγt mRNA increased, while the relative expression of IL-10 and Foxp3 mRNA decreased, and the differences were statistically significant ( t=-6.313,-5.922, 4.844, 7.572; P=0.003, 0.004, 0.008, 0.002). Compared with the LV-Ctrl group, the level of IL-17 in the serum of the mice in the LV-IL-23R group was significantly increased, and the difference was statistically significant ( t=-5.423, P=0.002); the proportion of Th17 cells in the spleen and lymph nodes was significantly increased, whereas, the proportion of Treg cells was significantly reduced, and the difference was statistically significant ( t=-4.290, 3.700; P=0.002, 0.006). Conclusion:IL-23R overexpression can promote Th17/Treg imbalance in EAU mice, and aggravate the clinical and pathological manifestations of EAU.