Profiling cellular heterogeneity in asthma with single cell multiparameter CyTOF.
Profiling cellular heterogeneity in asthma with single cell multiparameter CyTOF.
复制标题
DOI：
10.1002/jlb.5ma0720-770rr
复制
发表时间：
2020-11
影响因子：
5.5
通讯作者：
Montgomery RR
中科院分区：
文献类型：
--
作者：
Stewart E;Wang X;Chupp GL;Montgomery RR
哮喘是一种慢性气道炎症性疾病，美国有超过 3000 万人，全世界有超过 3 亿人患有哮喘。气道炎症反应通常通过痰液分析来表征，痰液中含有多种类型的细胞，包括中性粒细胞、巨噬细胞、淋巴细胞和罕见的支气管上皮细胞。使用痰显微镜对患者进行分型，发现气道炎症中存在中性粒细胞和嗜酸性粒细胞浸润。然而，由于这些细胞类型之间存在广泛的异质性，需要对痰中存在的炎症细胞类型有更高分辨率的了解，以剖析疾病的异质性。提高对哮喘粒细胞中不同表型和炎症来源的认识，可能会确定临床管理或新型治疗介质研究的相关途径。在这里，我们采用质谱流式细胞术或 CyTOF（飞行时间细胞术）来量化哮喘患者和健康对照中痰源气道细胞的频率并定义其功能状态。这项深入的单细胞分析确定了健康对照组和哮喘患者之间以及哮喘患者队列中气道免疫细胞的多种不同亚型，尤其是中性粒细胞。通过统计分析以及数据驱动的无偏聚类方法发现了显着性。我们的多维评估确定了细胞功能的差异，这些差异可能导致不同的临床反应，并为增进我们对哮喘炎症的了解提供有意义的见解。深入的单细胞分析可识别气道免疫细胞的多种不同亚型，并提供与哮喘发病机制相关的细胞功能的见解。
Asthma is a chronic inflammatory disease of the airways that afflicts over 30 million individuals in the United States and over 300 million individuals worldwide. The inflammatory response in the airways is often characterized by the analysis of sputum which contains multiple types of cells including neutrophils, macrophages, lymphocytes, and rare bronchial epithelial cells. Subtyping patients using microscopy of the sputum has identified both neutrophilic and eosinophilic infiltrates in airway inflammation. However, with the extensive heterogeneity among these cell types, a higher resolution understanding of the inflammatory cell types present in the sputum is needed to dissect the heterogeneity of disease. Improved recognition of the distinct phenotypes and sources of inflammation in asthmatic granulocytes, may identify relevant pathways for clinical management or investigation of novel therapeutic mediators. Here, we employed mass cytometry or CyTOF (Cytometry by Time-Of-Flight) to quantify frequency and define functional status of sputum derived airway cells in asthmatic patients and healthy controls. This in-depth single cell analysis identified multiple distinct subtypes of airway immune cells between healthy controls and asthmatic patients, and within an asthmatic patient cohort, especially in neutrophils. Significance was discovered by statistical analysis as well as a data-driven unbiased clustering approach. Our multidimensional assessment identifies differences in cellular function that may contribute to diverse clinical responses and provide meaningful insights to advance our knowledge of asthmatic inflammation. An in-depth single cell analysis identifies multiple distinct subtypes of airway immune cells and provides insights of cellular function relevant for pathogenesis of asthma.