慢性阻塞性肺疾病患者外周血Th17/CD25^+Foxp3^+Treg比率的变化

Change of Th17/CD25^+Foxp3^+ Treg ratio in peripheral blood of patients with chronic obstructive pulmonary disease and its significance

目的:研究慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者外周血中CD25^+Foxp3^+Treg和Th17细胞介导的免疫失衡与该疾病进展之间的相关性。方法:选择2012年1月至2015年3月在上海市闵行区江川社区及复旦大学附属上海市第五人民医院接受门诊或住院治疗的稳定期和急性发作期COPD患者共69例,同时收集吸烟或不吸烟的健康对照者各20例。测定受试者的肺功能。采用流式细胞术测定受试者外周血中Th17和CD25^+Foxp3^+Treg占CD4^+细胞的百分比,分析Th17/CD4^+和CD25^+Foxp3^+Treg/CD4^+比率以及Th17/CD25^+Foxp3^+Treg比值在不同分组中的变化及其临床意义。结果:与健康对照组相比,稳定期COPD患者外周血中Th17/CD4^+和Th17/CD25^+Foxp3^+Treg明显升高(P<0.05),而CD25^+Foxp3^+Treg/CD4^+明显降低(P<0.05);急性发作期COPD患者的Th17/CD4^+、CD25^+Foxp3^+Treg/CD4^+和Th17/CD25^+Foxp3^+Treg均比对照组明显升高(P<0.05)。轻度、中度、重度和极重度的COPD患者中Th17/CD4^+和Th17/CD25^+Foxp3^+Treg逐步升高(P<0.05),而CD25^+Foxp3^+Treg/CD4^+逐步降低(P<0.05);COPD患者的Th17/CD4^+和Th17/CD25^+Foxp3^+Treg与肺功能负相关(P<0.05),CD25^+Foxp3^+Treg/CD4^+与肺功能正相关(P<0.05)。结论:Th17/CD25^+Foxp3^+Treg失衡参与了COPD的疾病进展过程,提示Th17/CD25^+Foxp3^+Treg免疫调节治疗可能成为COPD治疗的新途径。

Objective ： To investigate the correlationship between peripheral CD25＋ Foxp3＋ Treg and T h l7 cellmediatedimmune imbalance and the progression of chronic obstructive pulmonary disease （COPD）. Methods： A total of sixtyninepatients with COPD in stable stage or acute exacerbation of COPD were recruited from Shanghai Fifth People‘’s Hospital ofFudan University from January 2012 to March 2015. At the same time, the non-smokers and smokers with normal lungfunction, each 20 cases, were also used as the healthy controls. The pulmonary function of all subjects was evaluated. Thepercentages of T h l7 and CD25＋ Foxp3＋Treg cells in CD4＋ cells from peripheral blood were determined by flow cytometry.The changes of Thl7/CD4＋ , CD25＋ Foxp3＋ Treg/CD4＋ and Thl7/CD25＋ Foxp3＋ Treg ratios in the different groups and theirclinical significance were analyzed. Results： Compared with the healthy control group, the ratios of Thl7/CD4＋ and T h l7/CD25＋ Foxp3＋ Treg in peripheral blood of patients with stable COPD were significantly increased （P〈C〇. 05） , while the ratio ofCD25＋ Foxp3＋ Treg/CD4＋ was significantly decreased （P〈C〇. 05）. The ratios of Thl7/CD4＋ , CD25＋ Foxp3＋ Treg/CD4＋ andThl7/CD25＋ Foxp3＋ Treg in patients with acute exacerbation of COPD were all increased as compared with the healthy control（all P〈C〇. 05）. With the decline of lung function, the ratios of Thl7/CD4＋ and Thl7/CD25＋ Foxp3＋ Treg were gradually upregulatedin patients with mild, moderate, severe, very severe COPD （P〈0. 0 5 ）, while the ratio of CD25＋ Foxp3＋ Tregpatients w ere negatively correlated w ith lung function （P 〈 0. 0 5 ） , w hile the ratio of C D 25＋ F o x p 3 ＋ T reg / C D 4＋ was positivelycorrelated w ith lung function （P 〈 C 0 . 0 5 ） . Conclusions： T h l7 / C D 2 5 ＋ F o x p 3 ＋ T re g im balance involves in the progression ofC O P D , suggesting th a t T h l7 / C D 2 5 ＋ Foxp 3＋ T re g imm unom odulatory therapy m ay becom e a new approach for the treatm en t ofCO PD.