调节性T细胞在多发性硬化中的免疫分子机制研究

Immune Molecular Mechanisms of Regulatory T Cells in the Pathogenesis of Multiple Sclerosis

目的研究和探索调节性T细胞在多发性硬化中的免疫分子机制。方法2014年1月至2015年1月，我院收集47例多发性硬化（multipleSclerosis，MS）患者为MS组，47例健康体检者为对照组，取肘静脉血并做如下检测和比较：①外周血单核细胞（periphery blood mononuclear cell，PBMC）中Treg细胞、Thl7细胞和Dc细胞数量；②Treg细胞、Th17细胞和Dc细胞功能相关基因mRNA表达水平；③外周血中Th17和Dc特异性促炎因子水平。结果在Ms患者中，①外周血中Treg细胞数量显著减少．Th17细胞和DC细胞数量显著增多，与对照组间具有显著统计学差异（P〈0．05）；②Treg细胞分化的关键转录因子FOXP3和FOXAI的mRNA表达水平显著降低，Th17细胞分化的关键转录因子RORyt、RORy和STAT3的mRNA表达水平显著增高，DC细胞分化的关键转录因子E2F1和PU．1的mRNA表达水平显著增高，与对照组间具有显著统计学差异（P〈0．05）；③Th17细胞特异性促炎因子IL-17和IL-22，DC细胞特异性促炎因子TNF-α、IL-12和IL-23的含量均显著高于对照组（P〈0．05）。结论MS患者外周血中Treg细胞减少、功能降低，受Treg细胞负调控的Th17细胞和Dc细胞增加，Th17细胞和Dc细胞分泌的促炎因子诱发一系列自身免疫级联反应，最终导致髓鞘脱失和轴突损害，引发一系列MS临床症状。

Objective To investigate the immune molecular mechanisms of regulatory T cells in the pathogenesis of multiple sclerosis （MS） . Methods A total of 47 MS patients （ MS group） and 47 healthy subjects （control group ） were recruited from Jan. 2014 to Jan. 2015. Blood was drawn from the cubital vein for detection of： （1） the number of Tregs, Thl7 cells and DCs in periph- ery blood mononuclear cells （PBMCs） of the peripheral blood; （2）mRNA levels of function related genes in Tregs, Thl7 cells and DCs; （3）levels of the specific inflammatory cytokines of Thl7 cells and DCs in the peripheral blood. Results （1） The number of Tregs cells in the periphery blood was dramatically decreased, and that of Thl7 cells and DCs was remarkably increased in MS group when compared with control group （P 〈 0.05 ） ; （2） the mRNA expression levels of the key transcription factors FOXP3 and FOXA1 during Treg differentiation were much lower and those of RORγ, RORγ and STAT3, the key transcription factors during TH17 differentiation, were significantly higher in MS group than in control group （P 〈 0.05 ） ; （3） the levels of the specific inflammatory cytokines of Thl7 cells and DCs such as IL-17, IL-22, TNF-α, IL-12 and IL-23 were significantly enhanced in MS group as compared with control group （P 〈 0. 05） . Conclusion In the MS patients, the num- ber of Tregs in the periphery blood is decreased and their function compromised, leading to the in- crease in Thl7 cells and DCs, which are negatively regulated by Tregs. The specific inflammatory cytokines secreted by Thl7 cells and DCs induce a series of autoimmune cascade reactions, resul- ting in the shedding of the myelin sheath, synapse injury and a range of clinical symptoms of MS.