Lower PDL1, PDL2, and AXL Expression on Lung Myeloid Cells Suggests Inflammatory Bias in Smoking and Chronic Obstructive Pulmonary Disease.
Lower PDL1, PDL2, and AXL Expression on Lung Myeloid Cells Suggests Inflammatory Bias in Smoking and Chronic Obstructive Pulmonary Disease.
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肺骨髓细胞上较低的 PDL1、PDL2 和 AXL 表达表明吸烟和慢性阻塞性肺疾病中存在炎症偏向。
DOI：
10.1165/rcmb.2020-0085oc
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发表时间：
2020
影响因子：
6.4
通讯作者：
Arjomandi,Mehrdad
中科院分区：
文献类型：
--
作者：
Vasudevan,Sreelakshmi;Vásquez,JoshuaJ;Chen,Wenxuan;Aguilar-Rodriguez,Brandon;Niemi,EreneC;Zeng,Siyang;Tamaki,Whitney;Nakamura,MaryC;Arjomandi,Mehrdad
肺骨髓细胞在肺免疫稳态和慢性阻塞性肺疾病（COPD）的发病机制中起重要作用。这些细胞的多参数免疫表型表征是具有挑战性的，因为它们的自发荧光和多样性。我们使用飞行时间质谱仪评估了COPD患者气道髓样细胞的免疫表型。使用44参数飞行时间质谱细胞术组检查来自BAL的细胞，这些细胞从从不吸烟者（n= 8）和具有（n= 20）和不具有（n= 4）肺量测定COPD的吸烟者获得。使用无监督聚类分析来鉴定通过手动门控确认的细胞亚型。我们确定了CD68+和CD68−细胞的主要群体，具有22个不同的表型簇，其中18个是髓系细胞。我们发现COPD患者的BAL中有较高丰度的推定募集的髓样细胞（CD68+经典单核细胞）。CD68+经典单核细胞群体对吸烟和COPD有不同的反应，这可能与其从血管和脉管系统中的募集有关。我们证明了来自吸烟者和COPD受试者的BAL细胞具有较低的AXL表达。此外，在COPD受试者中，我们报告了几种巨噬细胞亚型中PDL 1high和PDL 2high簇的丰度以及PDL 1和PDL 2的表达的显著差异，表明炎症反应的调节。此外，还发现了来自有COPD急性加重史受试者的BAL细胞中的几种表型差异，这些差异可能为潜在的疾病机制提供信息。总体而言，我们报告了吸烟、COPD和既往急性加重时发生的免疫表型景观的几种变化，这些变化与炎症通路的调节减少和激活增加一致。
Lung myeloid cells are important in pulmonary immune homeostasis and in the pathogenesis of chronic obstructive pulmonary disease (COPD). Multiparameter immunophenotypic characterization of these cells is challenging because of their autofluorescence and diversity. We evaluated the immunophenotypic landscape of airway myeloid cells in COPD using time of flight mass cytometry. Cells from BAL, which were obtained from never-smokers (n= 8) and smokers with (n= 20) and without (n= 4) spirometric COPD, were examined using a 44-parameter time of flight mass cytometry panel. Unsupervised cluster analysis was used to identify cellular subtypes that were confirmed by manual gating. We identified major populations of CD68+and CD68−cells with 22 distinct phenotypic clusters, of which 18 were myeloid cells. We found a higher abundance of putative recruited myeloid cells (CD68+classical monocytes) in BAL from patients with COPD. CD68+classical monocyte population had distinct responses to smoking and COPD that were potentially related to their recruitment from the interstitium and vasculature. We demonstrate that BAL cells from smokers and subjects with COPD have lower AXL expression. Also, among subjects with COPD, we report significant differences in the abundance of PDL1highand PDL2highclusters and in the expression of PDL1 and PDL2 across several macrophage subtypes suggesting modulation of inflammatory responses. In addition, several phenotypic differences in BAL cells from subjects with history of COPD exacerbation were identified that could inform potential disease mechanisms. Overall, we report several changes to the immunophenotypic landscape that occur with smoking, COPD, and past exacerbations that are consistent with decreased regulation and increased activation of inflammatory pathways.
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影响因子：
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DOI：
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发表时间：
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期刊：
影响因子：
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作者：
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影响因子：
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