Norton Dustin L, Ceppe Agathe, Tune Miriya K, McCravy Matthew, Devlin Thomas, Drummond M Bradley, Carson Shannon S, Vincent Benjamin G, Hagan Robert S, Dang Hong, Doerschuk Claire M, Mock Jason R
Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill, NC, USA.
Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
J Transl Med. 2020 Nov 11;18(1):427. doi: 10.1186/s12967-020-02595-3.
Foxp3 regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4 T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples.
We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48-96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4 T cells that were Tregs.
The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood.
Tregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4 cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target.
Foxp3调节性T细胞（Tregs）在免疫稳态及受损肺组织修复中发挥着重要作用。我们推测，以机械通气脱机时间衡量，肺损伤快速恢复的患者，其气道、支气管肺泡灌洗（BAL）或外周血样本中CD4 T细胞里Tregs的比例更高。
我们前瞻性纳入需要机械通气的急性呼吸窘迫综合征（ARDS）患者，并收集系列样本，第一份样本在ARDS诊断后72小时内（第0天）采集，第二份样本在48 - 96小时后（第3天）采集。我们分析了支气管镜检查时获取的BAL、气管吸出物和外周血中的免疫细胞群体及细胞因子，以及血浆中的细胞因子。根据所有参与者（n = 13）首次拔管的天数中位数，将研究队列分为快速恢复者（FR；n = 8）和缓慢恢复者（SR；n = 5）。主要测量指标是Tregs在CD4 T细胞中的百分比。
FR组的BAL中Tregs比SR组更多。这一发现并未扩展至气管吸出物或血液中的Tregs。与同时获取的外周血中的Tregs相比，BAL中的Tregs表达更多全长FOXP3，而非缺失外显子2的剪接变体。
ARDS期间支气管肺泡空间存在Tregs。FR组BAL中CD4细胞作为Tregs的百分比高于SR组。Tregs可能在ARDS的恢复中发挥作用，增加其数量或功能可能是一个治疗靶点。
