CAJ | 학술논문

目的探讨CD4+T细胞亚群间的免疫紊乱与溃疡性结肠炎(UC)发病的关系.方法收集24例UC患者(缓解期5例,活动期19例)及17名健康志愿者的外周血标本,分别作为病例组及对照组,提取外周血单个核细胞并采用流式细胞术检测CD4+T细胞各亚群的比例、采用荧光定量PCR检测各亚群相对应转录因子mRNA的表达,采用流式细胞微球技术(CBA)及酶联免疫吸附法(ELISA)检测各亚群主要细胞因子的蛋白表达水平.结果 (1) 病例组Treg细胞比例低于对照组(6.7%±1.7%比7.9%±1.4%,P=0.016),尤其是活动期为著(6.4%±1.7%,P=0.005),Treg细胞主要转录因子FOXP3 mRNA的表达低于对照组(P=0.020),其主要细胞因子转化生长因子(TGF)-β1在血清中的浓度亦低于对照组[(21±8) μg/L比(28±7) μg/L,P=0.026].(2) 病例组Th1细胞数目、其主要转录因子mRNA表达及主要细胞因子的蛋白水平均与对照组差异无统计学意义.(3)病例组Th2细胞比例高于对照组(2.7%±1.1%比1.6%±0.4%,P=0.002),尤其是活动期为著(2.8%±1.0%,P=0.001),Th2细胞主要转录因子GATA-3 mRNA的表达是对照组的4.4倍(P=0.045).(4)病例组Th17细胞比例高于对照组(3.4%±1.8% 比1.8%±0.7%,P=0.005),Th17细胞主要转录因子RORγt mRNA的表达约是对照组的13倍 (P=0.001); 其主要细胞因子IL-6和IL-17的表达亦均高于对照组 (均P<0.05).(5)病例组Treg/Th2和Treg/Th17均显著低于对照组且和活动度有关 (均P<0.05).结论 Treg、Th2和Th17细胞亚群间免疫失衡共同参与UC发病,可能是UC治疗新靶点.
목적 탐토CD4+T세포아군간적면역문란여궤양성결장염(UC)발병적관계.방법 수집24례UC환자(완해기5례,활동기19례)급17명건강지원자적외주혈표본,분별작위병례조급대조조,제취외주혈단개핵세포병채용류식세포술검측CD4+T세포각아군적비례、채용형광정량PCR검측각아군상대응전록인자mRNA적표체,채용류식세포미구기술(CBA)급매련면역흡부법(ELISA)검측각아군주요세포인자적단백표체수평.결과 (1) 병례조Treg세포비례저우대조조(6.7%±1.7%비7.9%±1.4%,P=0.016),우기시활동기위저(6.4%±1.7%,P=0.005),Treg세포주요전록인자FOXP3 mRNA적표체저우대조조(P=0.020),기주요세포인자전화생장인자(TGF)-β1재혈청중적농도역저우대조조[(21±8) μg/L비(28±7) μg/L,P=0.026].(2) 병례조Th1세포수목、기주요전록인자mRNA표체급주요세포인자적단백수평균여대조조차이무통계학의의.(3)병례조Th2세포비례고우대조조(2.7%±1.1%비1.6%±0.4%,P=0.002),우기시활동기위저(2.8%±1.0%,P=0.001),Th2세포주요전록인자GATA-3 mRNA적표체시대조조적4.4배(P=0.045).(4)병례조Th17세포비례고우대조조(3.4%±1.8% 비1.8%±0.7%,P=0.005),Th17세포주요전록인자RORγt mRNA적표체약시대조조적13배 (P=0.001); 기주요세포인자IL-6화IL-17적표체역균고우대조조 (균P<0.05).(5)병례조Treg/Th2화Treg/Th17균현저저우대조조차화활동도유관 (균P<0.05).결론 Treg、Th2화Th17세포아군간면역실형공동삼여UC발병,가능시UC치료신파점.
Objective To investigate the relationship of the imbalance of CD4+T cell subgroups and the pathogenesis of ulcerative colitis (UC).Methods Peripheral blood samples were collected from 24 UC patients and 17 healthy donors.Then the phenotype of CD4+T cells and the major transcription factor expression of each subset were analyzed by flow cytometry and real-time PCR (polymerase chain reaction) respectively.The serum concentrations of major cytokines of each subgroup were measured by cytometric bead array (CBA) and ELISA (enzyme-linked immunosorbent assay).Results (1) The proportion of Treg cells in the UC group was lower than the control group (6.7%±1.7% vs 7.9%±1.4%, P=0.016), especially in active stage (6.4%±1.7%, P=0.005). As compared with the control group, the expression of FOXP3 mRNA was lower in the UC Group (P=0.020). And so was the serum concentration of TGF-β1 [(21±8) μg/L vs (28±7) μg/L, P=0.026].(2)There were no significant differences in Th1-related transcription factors and cytokines between two groups.(3) Th2 cells were higher in the UC group (2.7%±1.1% vs 1.6%±0.4%, P=0.002), especially in active stage (2.8%±1.0%, P=0.001).The expression of GATA-3 mRNA was 4.4 folds higher than that of the controls (P=0.045).(4) Th17 cells were higher in the UC group (3.4%±1.8% vs 1.8%±0.7%, P=0.005). And the RORγt mRNA expression was 13 folds higher in UC group (P=0.001); the serum concentrations of IL-6 and IL-17 were higher in the UC group (both P<0.05). (5) The ratios of Treg/Th2 and Treg/Th17 were significantly lower in the UC group and associated with disease activity (both P<0.05).Conclusion The imbalances of Th2, Treg and Th17 subgroups may play pivotal roles in the pathogenesis of UC.