Airway macrophages display decreased expression of receptors mediating and regulating scavenging in early cystic fibrosis lung disease

作者：L. Slimmen, Vincent D. Giacalone, Craig Schofield, Hamed Horati, B. Manaï, Silvia Estevão, Luke W. Garratt, Limin Peng, Rabindra Tirouvanziam, Hettie M. Janssens, Wendy W. J. Unger · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1202009 · 被引用次数：8 · 研究领域：Cystic Fibrosis Research Advances、Neonatal Respiratory Health Research、Asthma and respiratory diseases

Background Cystic fibrosis (CF) airway disease is characterized by chronic inflammation, featuring neutrophil influx to the lumen. Airway macrophages (AMs) can promote both inflammation and resolution, and are thus critical to maintaining and restoring homeostasis. CF AM functions, specifically scavenging activity and resolution of inflammation, have been shown to be impaired, yet underlying processes remain unknown. We hypothesized that impaired CF AM function results from an altered expression of receptors that mediate or regulate scavenging, and set out to investigate changes in expression of these markers during the early stages of CF lung disease. Methods Bronchoalveolar lavage fluid (BALF) was collected from 50 children with CF aged 1, 3 or 5 years. BALF cells were analyzed using flow cytometry. Expression levels of surface markers on AMs were expressed as median fluorescence intensities (MFI) or percentage of AMs positive for these markers. The effect of age and neutrophilic inflammation, among other variables, on marker expression was assessed with a multivariate linear regression model. Results AM expression of scavenger receptor CD163 decreased with age (p = 0.016) and was negatively correlated with BALF %neutrophils (r = -0.34, p = 0.016). AM expression of immune checkpoint molecule SIRPα also decreased with age (p = 0.0006), but did not correlate with BALF %neutrophils. Percentage of AMs expressing lipid scavenger CD36 was low overall (mean 20.1% ± 16.5) and did n...