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支气管肺泡灌洗液中调节性 T 细胞、损伤相关分子模式和髓源抑制细胞与慢性阻塞性肺疾病严重程度的关联:一项观察性研究。

Regulatory T cells, damage-associated molecular patterns, and myeloid-derived suppressor cells in bronchoalveolar lavage fluid interlinked with chronic obstructive pulmonary disease severity: An observational study.

机构信息

Department of Pulmonology, Allergology and Pulmonary Oncology, Poznan University of Medical Sciences, Szamarzewskiego 84 Street, Poznan, Poland.

Department of Cancer Immunology, Poznan University of Medical Sciences, Garbary 15 Street, Poznan, Poland.

出版信息

Medicine (Baltimore). 2022 Jun 10;101(23):e29208. doi: 10.1097/MD.0000000000029208.

DOI:10.1097/MD.0000000000029208
PMID:35687771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9276103/
Abstract

The role of regulatory T cells (Tregs), damage-associated molecular patterns (DAMPs), and myeloid-derived suppressor cells (MDSCs) in the mechanism of innate and adaptive immune responses in chronic obstructive pulmonary disease (COPD) is not well understood.Evaluating the presence of Tregs in the bronchoalveolar lavage fluid (BALF) and peripheral blood in patients with COPD, and assessment of the relationship between Tregs, MDSCs, and DAMPs as factors activating innate and adaptive immune responses. Description of the association between immune and clinical parameters in COPD.Thirty-one patients with COPD were enrolled. Clinical parameters (forced expiratory volume in one second [FEV1], forced vital capacity, total lung capacity [TLC], diffusion capacity of carbon monoxide, and B-BMI, O-obstruction, D-dyspnea, E-exercise [BODE]) were assessed. Tregs and MDSCs were investigated in the BALF and blood using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. The levels of defensin (DEF2), galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-9 (Gal-9), heat shock protein-27 (HSP27), and surfactant protein A were assessed via sandwich enzyme-linked immunosorbent assay.The percentage of Tregs was significantly higher in the blood than in the BALF, in contrast to the mean fluorescence intensity of forkhead box P3 (FoxP3). Significant associations were observed between Tregs and HSP27 (r = 0.39), Gal-1 (r = 0.55), Gal-9 (r = -0.46), and MDSCs (r = -0.50), and between FoxP3 and Gal-1 (r = -0.42), Gal-3 (r = -0.39), and MDSCs (r = -0.43). Tregs and clinical parameters, including FEV1%pred (r = 0.39), residual volume (RV)%pred (r = -0.56), TLC%pred (r = -0.55), RV/TLC (r = -0.50), arterial oxygen saturation (r = -0.38), and arterial oxygen pressure (r = -0.39) were significantly correlated. FoxP3 was significantly interlinked with RV/TLC (r = -0.52), arterial oxygen pressure (r = 0.42), and BODE index (r = -0.57).The interaction between innate and adaptive immune responses in patients with COPD was confirmed. The expression of Tregs in BALF may have prognostic value in patients with COPD. The conversion of immune responses to clinical parameters appears to be associated with disease severity.

摘要

调节性 T 细胞(Tregs)、损伤相关分子模式(DAMPs)和髓系来源抑制细胞(MDSCs)在慢性阻塞性肺疾病(COPD)固有和适应性免疫反应机制中的作用尚不清楚。评估 COPD 患者支气管肺泡灌洗液(BALF)和外周血中 Tregs 的存在,并评估 Tregs、MDSCs 和 DAMPs 作为激活固有和适应性免疫反应的因素之间的关系。描述 COPD 中免疫和临床参数之间的关联。共纳入 31 例 COPD 患者。评估临床参数(一秒用力呼气量[FEV1]、用力肺活量、肺总量[TLC]、一氧化碳弥散量和 B-BODE[体重指数、阻塞、呼吸困难、运动])。使用流式细胞术直接与荧光染料偶联的单克隆抗体在 BALF 和血液中研究 Tregs 和 MDSCs。通过夹心酶联免疫吸附试验评估防御素(DEF2)、半乳糖凝集素-1(Gal-1)、半乳糖凝集素-3(Gal-3)、半乳糖凝集素-9(Gal-9)、热休克蛋白 27(HSP27)和表面活性蛋白 A 的水平。Tregs 在血液中的百分比明显高于 BALF,而叉头框 P3(FoxP3)的平均荧光强度则相反。Tregs 与 HSP27(r=0.39)、Gal-1(r=0.55)、Gal-9(r=-0.46)和 MDSCs(r=-0.50)之间存在显著相关性,FoxP3 与 Gal-1(r=-0.42)、Gal-3(r=-0.39)和 MDSCs(r=-0.43)之间存在显著相关性。Tregs 与临床参数,包括 FEV1%pred(r=0.39)、残气量(RV)%pred(r=-0.56)、TLC%pred(r=-0.55)、RV/TLC(r=-0.50)、动脉血氧饱和度(r=-0.38)和动脉血氧分压(r=-0.39)呈显著相关。FoxP3 与 RV/TLC(r=-0.52)、动脉血氧分压(r=0.42)和 BODE 指数(r=-0.57)呈显著相关。COPD 患者固有和适应性免疫反应之间的相互作用得到了证实。BALF 中 Tregs 的表达可能对 COPD 患者具有预后价值。免疫反应向临床参数的转化似乎与疾病严重程度有关。

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