Abstract
BackgroundChronic Obstructive Pulmonary Disease (COPD) is associated with an abnormal pulmonary and systemic immune response to tobacco smoking. Yet, how do immune cells relate within and between these two biological compartments, how the pulmonary infiltrate influences the lung transcriptome, and what is the role of active smoking vs. presence of disease is unclear.MethodsTo investigate these questions, we simultaneously collected lung tissue and blood from 65 individuals stratified by smoking habit and presence of the disease. The immune cell composition of both tissues was assessed by flow cytometry, whole lung transcriptome was determined with Affymetrix arrays, and we used Weighted Gene Co-expression Network Analysis (WGCNA) to integrate results.ResultsMain results showed that: (1) current smoking and the presence of COPD were both independently associated with a reduction in the proportion of lung T cells and an increase of macrophages, specifically those expressing CD80 + CD163+; (2) changes in the proportion of infiltrating macrophages, smoking status or the level of airflow limitation were associated to different WGCNA modules, which were enriched in iron ion transport, extracellular matrix and cilium organization gene ontologies; and, (3) circulating white blood cells counts were correlated with lung macrophages and T cells.ConclusionsMild-moderated COPD lung immune infiltrate is associated with the active smoking status and presence of disease; is associated with changes in whole lung tissue transcriptome and marginally reflected in blood.
Highlights
Chronic Obstructive Pulmonary Disease (COPD) is associated with an abnormal pulmonary and systemic immune response to tobacco smoking
We hypothesized that a data set that combined lung tissue and circulating blood measurements collected simultaneously in current and former smokers with COPD, as well as controls with normal lung function, would be a unique asset to: (1) characterize the lung and blood immune cell composition in relation to both smoking status and presence of disease; (2) explore the relationship between the lung immune cell composition and the lung tissue transcriptome; and, (3) construct a multi-level immune cell correlation network to assess if the lung changes are reflected in the blood
To interpret them appropriately, it is important to consider that: (1) because our methodology does not allow the quantification of the absolute number of infiltrating cells, our results refer to their relative proportion; (2) we studied patients with mild-moderate, not severe-very severe, COPD
Summary
Chronic Obstructive Pulmonary Disease (COPD) is associated with an abnormal pulmonary and systemic immune response to tobacco smoking. How do immune cells relate within and between these two biological compartments, how the pulmonary infiltrate influences the lung transcriptome, and what is the role of active smoking vs presence of disease is unclear. We hypothesized that a data set that combined lung tissue and circulating blood measurements collected simultaneously in current and former smokers with COPD, as well as controls with normal lung function (current and never smokers), would be a unique asset to: (1) characterize the lung and blood immune cell composition in relation to both smoking status and presence of disease; (2) explore the relationship between the lung immune cell composition and the lung tissue transcriptome; and, (3) construct a multi-level (lung and blood) immune cell correlation network to assess if the lung changes are reflected in the blood. The plasma concentration of high sensitivity C Reactive Protein (hsCRP) was determined by ultra-sensitive quantitative turbidimetric test (Bayer Diagnostics, Germany)
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