Tao Xuefang, Tian Hai, Wang Guowen, Sun Yongzhen, Zhao Liangyan
Department of Respiratory Medicine, The Affiliated Hospital of ShaoXing University, No. 999, Zhongxing South Road, Yuecheng District, Shaoxing, 312000, Zhejiang, China.
Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, 312000, Zhejiang, China.
BMC Pulm Med. 2025 Apr 14;25(1):181. doi: 10.1186/s12890-025-03632-x.
Chronic obstructive pulmonary disease (COPD) is a common disease with respiratory symptoms and limited airflow. Exosomes derived from Tregs (Treg-exo) could regulate immune function and prevent autoimmune disease. This study assessed Treg-exo effects on COPD.
In vivo, rats were divided into three groups including control, COPD and exosomes groups. COPD models were established by passive smoking combined with lipopolysaccharide. Phosphate buffered saline or Treg-exo were administered via tail vein. Lung function, Hematoxylin and Eosin staining, and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate lung function, histopathology and inflammation. Flow cytometry was used for peripheral blood T cell separation and counting. In vitro, COPD cluster of differentiation (CD) 4 T-cells were isolated from spleen and co-cultured with Treg-exo alone or in combination with Colivelin (a signal transducer and activator of transcription 3/STAT3 activator). Flow cytometry, ELISA, and Western blot were used to count T helper cell 17 (Th17) and detected cytokines and STAT3 proteins expression.
In vivo, pulmonary function tests and HE staining showed Treg-exo treatment enhanced lung function and alleviated lung damage; flow cytometry showed Treg-exo treatment decreased CD8, CD4 CD25 cells and Th17; ELISA assay found Treg-exo treatment increased transforming growth factor-β and interleukin (IL)-10 and decreased tumor necrosis factor-α and IL-8 in serum, broncho alveolar lavage fluid, and lung tissue. In vitro, Treg-exo treatment inhibited Th17 differentiation and suppressed the content of IL-6, IL-17, and IL-23 and STAT3 phosphorylation.
Treg-exo suppressed inflammation and CD4 T-cell differentiation to Th17, possibly by inhibiting STAT3 phosphorylation.
慢性阻塞性肺疾病（COPD）是一种具有呼吸道症状且气流受限的常见疾病。来自调节性T细胞的外泌体（Treg-exo）可调节免疫功能并预防自身免疫性疾病。本研究评估了Treg-exo对COPD的影响。
在体内，将大鼠分为三组，包括对照组、COPD组和外泌体组。通过被动吸烟联合脂多糖建立COPD模型。经尾静脉注射磷酸盐缓冲盐水或Treg-exo。进行肺功能、苏木精-伊红染色和酶联免疫吸附测定（ELISA）以评估肺功能、组织病理学和炎症。采用流式细胞术对外周血T细胞进行分离和计数。在体外，从脾脏中分离出COPD分化簇（CD）4 T细胞，并单独或与可立维林（一种信号转导和转录激活因子3/STAT3激活剂）联合与Treg-exo共培养。采用流式细胞术、ELISA和蛋白质免疫印迹法对辅助性T细胞17（Th17）进行计数，并检测细胞因子和STAT3蛋白表达。
在体内，肺功能测试和HE染色显示Treg-exo治疗可改善肺功能并减轻肺损伤；流式细胞术显示Treg-exo治疗可降低CD8、CD4 CD25细胞和Th17；ELISA检测发现Treg-exo治疗可使血清中、支气管肺泡灌洗液和肺组织中的转化生长因子-β和白细胞介素（IL）-10增加，肿瘤坏死因子-α和IL-8减少。在体外，Treg-exo治疗可抑制Th17分化，并抑制IL-6、IL-十七和IL-23的含量以及STAT3磷酸化。
Treg-exo可能通过抑制STAT3磷酸化来抑制炎症和CD4 T细胞向Th17分化。
