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Unique natural killer cell subpopulations are associated with exacerbation risk in chronic obstructive pulmonary disease.
Scientific Reports ( IF 4.6 ) Pub Date : 2020-01-27 , DOI: 10.1038/s41598-020-58326-7
Andrew R Osterburg 1 , Laura Lach 2 , Ralph J Panos 1, 2 , Michael T Borchers 1, 2
Affiliation  

Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death worldwide. COPD is frequently punctuated by acute exacerbations that are precipitated primarily by infections, which increase both morbidity and mortality and inflates healthcare costs. Despite the significance of exacerbations, little understanding of immune function in COPD exacerbations exists. Natural killer (NK) cells are important effectors of innate and adaptive immune responses to pathogens and NK cell function is altered in smokers and COPD. Using high-dimensional flow cytometry, we phenotyped peripheral blood NK cells from never smokers, smokers, and COPD patients and employed a non-supervised clustering algorithm to define and detect changes in NK cell populations. We identified greater than 1,000 unique NK cell subpopulations across patient groups and describe 13 altered NK populations in patients who experienced prior exacerbations. Based upon cluster sizes and associated fluorescence data, we generated a logistic regression model to predict patients with a history of exacerbations with high sensitivity and specificity. Moreover, highly enriched NK cell subpopulations implicated in the regression model exhibited enhanced effector functions as defined by in vitro cytotoxicity assays. These novel data reflect the effects of smoking and disease on peripheral blood NK cell phenotypes, provide insight into the potential immune pathophysiology of COPD exacerbations, and indicate that NK cell phenotyping may be a useful and biologically relevant marker to predict COPD exacerbations.

中文翻译:

独特的自然杀伤细胞亚群与慢性阻塞性肺疾病的恶化风险相关。

慢性阻塞性肺疾病(COPD)是全球第三大死亡原因。COPD经常因急性加重而突然发作,而急性加重主要是由感染引起的,这会增加发病率和死亡率,并增加医疗费用。尽管恶化的重要性,但对COPD恶化中免疫功能的了解很少。天然杀伤(NK)细胞是对病原体的先天性和适应性免疫反应的重要效应子,吸烟者和COPD中的NK细胞功能发生了变化。我们使用高维流式细胞仪对从未吸烟者,吸烟者和COPD患者的外周血NK细胞进行了表型分析,并采用非监督聚类算法来定义和检测NK细胞群体的变化。我们确定大于1 跨患者群体的000个独特的NK细胞亚群,描述了经历过急性加重的患者中13个改变的NK群体。基于簇的大小和相关的荧光数据,我们生成了一个逻辑回归模型,以高敏感性和特异性预测有急性发作史的患者。此外,涉及到回归模型的高度富集的NK细胞亚群表现出增强的效应子功能,如体外细胞毒性试验所定义。这些新颖的数据反映了吸烟和疾病对外周血NK细胞表型的影响,提供了对COPD急性发作的潜在免疫病理生理学的洞察力,并表明NK细胞表型可能是预测COPD急性发作的有用且生物学相关的标志物。
更新日期:2020-01-27
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