Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality

• Published in: Frontiers in immunology 2021-11, Vol.12, p.645548-645548
• Main Authors: Tsitoura, Eliza, Trachalaki, Athina, Vasarmidi, Eirini, Mastrodemou, Semeli, Margaritopoulos, George A, Kokosi, Maria, Fanidis, Dionysios, Galaris, Apostolos, Aidinis, Vassilis, Renzoni, Elizabeth, Tzanakis, Nikos, Wells, Athol U, Antoniou, Katerina M
• Format: Article
• Language: English
• Subjects: Adult; Aged; airway macrophages; Animals; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Case-Control Studies; Collagen Type I, alpha 1 Chain - genetics; Collagen Type I, alpha 1 Chain - metabolism; Disease Models, Animal; Disease Progression; Female; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis - metabolism; Idiopathic Pulmonary Fibrosis - mortality; Idiopathic Pulmonary Fibrosis - pathology; Immunology; IPF; Lung - metabolism; Lung - pathology; Lung - physiopathology; Lung Diseases, Interstitial - metabolism; Lung Diseases, Interstitial - mortality; Lung Diseases, Interstitial - pathology; Macrophages, Alveolar - metabolism; Male; Mice; Middle Aged; NSIP; osteopontin; Osteopontin - genetics; Osteopontin - metabolism; Prospective Studies; RA-ILD; RNA, Messenger - genetics; RNA, Messenger - metabolism; SPP1; Vital Capacity
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.645548

Within the Interstitial Lung Diseases (ILD), patients with idiopathic pulmonary fibrosis (IPF) and a subset of those with non-IPF fibrotic ILD have a distinct clinical phenotype of progression despite management. This group of patients has been collectively termed the progressive fibrotic phenotype (PFP). Their early recognition may facilitate access to antifibrotic therapies to prevent or slow progression. Macrophages/monocytes within the lung orchestrate the progression and maintenance of fibrosis. A novel role for monocyte-derived macrophages during tissue damage and wound healing is the expression of collagens. We examined Collagen 1a1 expression in airway macrophages from ILD patients at diagnosis. COL1A1 mRNA levels from BAL cells were elevated in IPF and Non-IPF patients. The presence of a UIP pattern and a subsequent progressive phenotype were significantly associated with the higher BAL COL1A1 levels. In Non-IPF patients, higher COL1A1 levels were associated with a more than twofold increase in mortality. The intracellular localisation of COL1A1 in airway macrophages was demonstrated by confocal microscopy in CD45 and CD163 co-staining assays. Additionally, airway macrophages co-expressed COL1A1 with the profibrotic SPP1 gene product osteopontin. The levels of SPP1 mRNA and OPN in the BAL were significantly higher in IPF and Non-IPF patients relative to healthy. Our results suggest that profibrotic airway macrophages are increased in the BAL of patients with IPF and other ILDs and co-express COL1A1 and OPN. Importantly, COL1A1 expression by pro-fibrotic airway macrophages could be a marker of disease progression and poor survival in ILDs.