Th17/Treg细胞及相关细胞因子在复发缓解型多发性硬化中的作用及机制  

Role of Th17/Treg cells and related cytokines in patients with relapsing remitting multiple sclerosis

作　　者：李丹 王黙 纪元[1] 王玮[1] 袁晓燕[1] LI Dan;WANG Mo;JI Yuan;WANG Wei;YUAN Xiaoyan(Department of Clinical Laboratory,Weihai Municipal Hospital,Weihai Shandong,264200,China)

机构地区：[1]威海市立医院检验科,264200 [2]山东大学附属省立医院血管外科,250021

出　　处：《中国神经免疫学和神经病学杂志》2019年第2期89-93,98,共6页Chinese Journal of Neuroimmunology and Neurology

基　　金：山东省重点研发计划项目(2016GSF201227)

摘　　要：目的探讨辅助性T细胞(Th17)、调节性T细胞(Treg)和相关细胞因子在复发缓解型多发性硬化(RRMS)患者发病机制中的作用与机制。方法收集急性期RRMS患者(RRMS组)31例,以神经系统非炎性疾病29例为对照组。RRMS患者入院后给予静脉滴注甲泼尼龙1000 mg/d冲击治疗,后续每3 d剂量减半。对RRMS组患者治疗前和甲泼尼龙治疗2周后(治疗后)分别进行残疾状况拓展性量表(EDSS)评分;采用流式细胞术(FCM)检测RRMS组患者治疗前后及对照组患者外周血Th17(CD4^+IL-17^+)细胞和Treg(CD4^+FOXP3^+)细胞百分率;采用酶联免疫吸附试验(ELISA)检测RRMS组患者治疗前后及对照组患者外周血血浆中白细胞介素(IL)-17A、IL-23、IL-6、IL-10、IL-35和转化生长因子-β(TGF-β)水平;采用Spearman相关分析对RRMS组患者治疗前外周血Th17细胞数量与IL-17A、IL-23、IL-35、IL-6、IL-10及TGF-β水平进行相关性分析。结果 (1)RRMS组治疗前EDSS评分高于治疗后[分别(6.31±1.54)分vs.(4.02±0.68)分,t=0.75,P<0.05];(2)FCM分析结果显示,与对照组[(3.12±1.27)%]比较,RRMS组患者治疗前Th17细胞百分率[(15.24±2.54)%]明显升高(P<0.05),而对照组Treg细胞百分率[(35.04±4.21)%]明显高于RRMS组治疗前[(11.12±3.13)%,P<0.05];与对照组(0.10±0.02)相比,RRMS组治疗前Th17/Treg(1.51±0.62)也明显升高(P<0.01);与RRMS组治疗前[(11.12±3.13)%]比较,甲泼尼龙治疗后Treg细胞比例[(23.14±2.86)%]明显升高(P<0.01);与RRMS组治疗前Th17细胞百分率[(15.24±2.54)%]相比,甲泼尼龙治疗后Th17细胞百分率[(4.24±1.14)%]明显降低(t=0.88,P<0.05);与RRMS组治疗前(1.51±0.62)相比,甲泼尼龙治疗后Th17/Treg比值(0.19±0.07)降低(t=0.95,P<0.01);(3)ELISA法检测结果显示,RRMS组治疗前IL-17A[分别(17.26±1.21)pg/mL vs.(3.23±0.81)pg/mL,t=0.72,P<0.05]、IL-23[(分别(64.38±7.51)pg/mL vs.(21.14±1.82)pg/mL,t=0.75,P<0.05]、IL-6[分别(70.14±8.17)pg/mL vs.(7.28±0.75)pg/mL,t=0.95,P<0.01]和IL-10水平[分别(21.Objective To investigate the role of helper T cells (Th17), regulatory T cells (Treg) and related cytokines in the pathogenesis of RRMS. Methods Thirty-one patients with acute RRMS relapses(the RRMS group) were collected, and 29 patients with non-inflammatory neurological diseases were selected as the control group.After admission, RRMS patients were treated with intravenous infusion of methylprednisolone at 1000 mg/d and the subsequent doses was halved every 3 days.Patients in the RRMS group were evaluated by the extended disability scale (EDSS) before treatment and after 2 weeks of treatment with methylprednisolone.Flow cytometry (FCM) was used to detect the percentage of CD4^+IL-17^+cells and CD4^+FOXP3^+cells in peripheral blood of the RRMS group before and after treatment as well as the control group.Serum levels of interleukin (IL-17A, IL-23,IL-6,IL-10,IL-35 and transforming growth factor-β(TGF-β) in RRMS group and the control group were detected by ELISA before and after treatment.Spearman correlation analysis was used to analyze the correlation between the number of Th17 cells in peripheral blood and the levels of IL-17A,IL-23, IL-35, IL-6, IL-10 and TGF-β. in the RRMS group before treatment. Results (1) The pre-treatment EDSS score in the RRMS group was higher than that after treatment[(6.31±1.54) vs.(4.02±0.68), t =0.75, P <0.05].(2) The results of the FCM analysis showed that compared with the control group [(3.12±1.27)%], the percentage of Th17 cells [(15.24±2.54)%] in the RRMS group before treatment was significantly increased (P <0.05), while the percentage of Treg cells in the RRMS group before treatment was significantly lower [(11.12±3.13)% vs .(35.04±4.21)%, P <0.01].The Th17/Treg ratio of the RRMS group[(1.51±0.62)%] also significantly increased before treatment , compared with the control group [(0.10±0.02)%]( P <0.01). Compared with the RRMS group before treatment [(11.12 ±3.13)%], the percentage of Treg cells[(23.14±2.86)%] after methylprednisolone treatment was significantly in

关 键 词：多发性硬化 TH17细胞 TREG细胞 白细胞介素-17 

分 类 号：R744.51[医药卫生—神经病学与精神病学]