变应原和糖皮质激素对变应性鼻炎患者外周血Th17细胞及其转录因子RORγt的作用

摘要

目的 了解变应原和糖皮质激素对变应性鼻炎(allergic rhiaitis,AR)成人患者外周血新型辅助性T细胞17(T help 17,Th17)及其转录因子孤独受体(retinoid-related orphan nuclear receptor,RORγt)mRNA表达水平以及白细胞介素(inter leukin,IL)23、IL-6和IL-17水平的影响.方法 40例AR患者(A组)随机分为2组,每组20例.第1组(A1组)给予经鼻吸入糖皮质激素(intranasal glucocorticoid,INGS)治疗4周,第2组(A2组)给予特异性免疫治疗(special immunotherapy,SIT)1年.分别取治疗前后2组患者和另10例健康对照者(B组)外周血,用流式细胞术检测Th17细胞阳性率;用反转录聚合酶链反应(RT-PCR)法检测RORγt mRNA表达水平;用酶联免疫吸附(ELISA)法检测培养上清液中IL-23、IL-6和IL-17水平.结果 A组患者外周血中Th17细胞阳性率、RORγt mRNA的相对表达量(x-±s,以下同)分别为(18.97±1.05)%和(0.604±0.027),高于B组的(15.12±1.09)%和(0.447±0.024),差异有统计学意义(t值分别为-10.056和-17.986,P值均＜0.01).A组患者IL-6、IL-17和IL-23水平均高于B组,差异有统计学意义(t值分别为-41.149、-17.618和-26.824,P值均＜0.01).A1组治疗前后Th17细胞阳性率、RORγt mRNA的相对表达量、IL-6、IL-17和IL-23水平5项指标差异均无统计学意义(t值分别为0.298、0.240、-1.136、0.283和-1.670,P值均＞0.05).A2组SIT治疗前外周血中Th17细胞阳性率、RORγt mRNA的相对表达量分别为(18.99±1.14)%和(0.603±0.027),高于治疗后的(16.30±1.63)%和(0.429±0.023),差异有统计学意义(t值分别为6.035和22.015,P值均＜0.01).A2组SIT治疗后IL-6、IL-17和IL-23水平显著下降,与治疗前相比差异有统计学意义(t值分别为9.235、11.289、7.267,P值均＜0.01).结论 AR患者Th17细胞数量、RORγt mRNA的表达量以及相应的细胞因子IL-23、IL-6和IL-17水平上调,SIT治疗可以使以上5项指标下降,而INGS治疗对以上5项指标没有影响.%Objective To study the effect of specific immunotherapy and intranasal glucocorticoid on T help 17(Th17)cells and RORγt in peripheral blood in patients with allergic rhinitis(AR).Methods Forty patients with allergic rhinitis(group A)were divided randomly into two subgroups(group A1 and A2),and each subgroup had 20 patients.The patients in group A1 were treated with intranasal glucocorticoid(INGS)for one-year.The patients in group A2 were treated with special immunotherapy (SIT)for 4 weeks.Blood samples were respectively taken from 10 healthy individuals(group B),20 AR patients(group A1)before and after SIT with specific standardized allergen and 20 AR patients(group A2)before and after INGS.The ratio of Th17 cells in peripheral blood monouclear cells(PBMC)were analysed by flow cytometry.The expression of RORγt mRNA were detected by real-time polymerase chain reaction and the interleukin-23(IL-23),IL-17,IL-6 were detected by enzyme-linked immunosorbent assay.Results The ratio of Th17 cells in PBMC and the expression of RORγt mRNA in group A[(18.97 ± 1.05)% and (0.604 ± 0.027)]were respectively higher than those in group B[(15.12 ± 1.09)% and(0.447 ±0.024)]and the difference reached statistical significance(t were respectively-10.056 and-17.986,each P＜0.01).The level of IL-6,IL-17 and IL-23 in group A were respectively higher than those in group B and the difference reached statistical significance(t were respectively-41.149,-17.618 and -26.824,all P＜0.01).The ratio of Th17 cells in PBMC,the expression of RORγt mRNA,the level of IL-6,IL-17 and IL-23 before INGS did not show significant difference from those of after INGS in group A1 (t were respectively 0.298,0.240,-1.136,0.283 and-1.670,all P＞0.05).The ratio of Th 17 cells in PBMC and the expression of RORγt mRNA were respectively(18.99 ± 1.14)% and(0.603 ± 0.027)before SIT and were respectively(16.30 ± 1.63)% and(0.429 ± 0.023)after SIT in group A2,and the difference reached statistical significance(t were respectively 6.035 and 22.015,all P＜0.01).The level of IL-6,IL-17 and IL-23 before SIT were lower respectively than those of after SIT in group A2 and the difference reached statistical significance(t were respectively 9.235,11.289,7.267,all P＜0.01).Conclusions The ratio of Th17 cells in PBMC,the expression of ROR-yt mRNA,the level of IL-6,IL-17 and IL-23 were up-regulated in patients with AR.The treatment of SIT could get the 5 items down and the treatment of INGS couldn't.