CAJ | 학술논문

目的观察辅助性T细胞17(Th17细胞)-调节T(Treg)细胞平衡在系统性红斑狼疮(SLE)患者外周血中的变化及探讨其临床意义.方法选取活动期和稳定期SLE患者各40例,健康志愿者20例为研究对象.运用流式细胞术检测外周血中Th17细胞和Treg细胞,分析SLE患者外周血中Th17细胞/Treg细胞比例的变化及其与疾病活动的相关性.同时用实时荧光定量PCR方法检测Th17细胞和Treg细胞相关调控基因维甲酸相关孤核受体(ROR-γt)mRNA和叉头翼螺旋转录因子(Foxp3)mRNA在外周血单个核细胞(PBMC)上的表达.结果活动期SLE患者外周血Th17细胞的比例[(1.86±0.96)％]高于稳定期SLE患者[(1.05±0.40)％,P＜0.01]和健康对照组[(0.80±0.33)％,P＜0.01],而CD4+CD25+Foxp3+Treg细胞的比例[(1.95±0.85)％]低于稳定期SLE患者[(4.22±1.34)％,P＜0.01]和健康对照组[(6.04±1.49)％,P＜0.01];Th17细胞/Treg细胞比值在活动期SLE患者为(0.97±0.55),较稳定期SLE患者(0.25±0.38)(P＜0.01)和健康对照组(0.13±0.07)(P＜0.01)升高,并与SLE活动指数评分成正相关(r=0.69,P＜0.01).SLE患者PBMC上ROR-γt mRNA的表达(7.61±5.39)较健康对照组(3.51±3.52)增多(P＜0.05),Foxp3 mRNA的表达(4.67±4.23)较健康对照组(11.67±5.09)减少(P＜0.05).结论活动期SLE患者外周血Th17细胞及相关调控基因ROR-γt mRNA的表达升高,Treg细胞及相关调控基因Foxp3 mRNA的表达下降,存在Th17细胞/Treg细胞比例失衡,提示Th17细胞分化增多,伴随Treg细胞减少,可导致SLE发病.
목적 관찰보조성T세포17(Th17세포)-조절T(Treg)세포평형재계통성홍반랑창(SLE)환자외주혈중적변화급탐토기림상의의.방법 선취활동기화은정기SLE환자각40례,건강지원자20례위연구대상.운용류식세포술검측외주혈중Th17세포화Treg세포,분석SLE환자외주혈중Th17세포/Treg세포비례적변화급기여질병활동적상관성.동시용실시형광정량PCR방법검측Th17세포화Treg세포상관조공기인유갑산상관고핵수체(ROR-γt)mRNA화차두익라선전록인자(Foxp3)mRNA재외주혈단개핵세포(PBMC)상적표체.결과 활동기SLE환자외주혈Th17세포적비례[(1.86±0.96)％]고우은정기SLE환자[(1.05±0.40)％,P＜0.01]화건강대조조[(0.80±0.33)％,P＜0.01],이CD4+CD25+Foxp3+Treg세포적비례[(1.95±0.85)％]저우은정기SLE환자[(4.22±1.34)％,P＜0.01]화건강대조조[(6.04±1.49)％,P＜0.01];Th17세포/Treg세포비치재활동기SLE환자위(0.97±0.55),교은정기SLE환자(0.25±0.38)(P＜0.01)화건강대조조(0.13±0.07)(P＜0.01)승고,병여SLE활동지수평분성정상관(r=0.69,P＜0.01).SLE환자PBMC상ROR-γt mRNA적표체(7.61±5.39)교건강대조조(3.51±3.52)증다(P＜0.05),Foxp3 mRNA적표체(4.67±4.23)교건강대조조(11.67±5.09)감소(P＜0.05).결론 활동기SLE환자외주혈Th17세포급상관조공기인ROR-γt mRNA적표체승고,Treg세포급상관조공기인Foxp3 mRNA적표체하강,존재Th17세포/Treg세포비례실형,제시Th17세포분화증다,반수Treg세포감소,가도치SLE발병.
Objective To investigate the changes and clinical significance of the equilibrium of peripheral blood helper T cell 17 (Th17)-regulatory T cell (Treg) in patients with systemic lupus erythematosus (SLE).Methods Forty patients with active SLE,40 clinically stable SLE patienls and 20 healthy volunteers were enrolled in this study.Changes in peripheral blood Th17/Treg cell ratio and its correlation with disease activity were determined following detection of Th17 cells and Treg cells by flow cytometry.Real-time fluorescent quantitative PCR was employed to examine the expression of retinoic acid related solitary nucleus receptor (RORγt) and fork wing spiral transcription factor (Foxp3) mRNAs,the genes that govern regulation of Th17 and Treg cells,in peripheral mononuclear cell (PBMC).Results Patients with active SLE had higher percentage of Th17 cells in peripheral blood compared with those without active SLE [(1.86±0.96) ％ vs (1.05±0.40)％,P＜0.01] and healthy controls [(0.80±0.33)％,P<0.01],and lower percentage of CD4-CD25+Foxp3+Treg cells compared with those without active SLE [(1.95±0.85) ％ vs (4.22± 1.34)％,P＜0.01] and healthy controls [(6.04+1.49)％,P＜0.01].The ratio of Th17/Treg cells increased during the active state when compared with clinically stable period [(0.97±0.55) vs (0.25±0.38),P＜0.01] and healthy controls [(0.13±0.07),P＜0.O1],which was positively correlated with SLE disease activity index score (r=0.69,P＜0.01).Furthermore,SLE patients presented higher RORγt mRNA expression [(7.61±5.39) vs (3.51±3.52),P＜0.05] and lower Foxp3 mRNA expression ([4.67±4.23] vs [11.67±5.09],P＜0.05) as compared with healthy controls.Conclusion Patients with active SLE have more Th17 cells and up-regulating RORγt mRNA expression,but less Treg cells and down-regulating Foxp3 mRNA expression leading to imbalance of Th17/Treg cell ratio in peripheral blood.Increased differentiated Th17 cell count and reduced Foxp3 mRNA may be involved in the pathogenesis of SLE.