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

Abstract

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.

Integrated characterization of cell types, states and molecular programs in disseminated appendiceal neoplasms

“…Interestingly, macrophages from cancerous tissues, especially from LGMA tissues, express high levels of collagen genes ( COL1A1, COL1A2 and COL3A1 ) (Fig. 4g-h), a phenotype previously reported in the airway macrophages of the fibrotic lungs 45 .…”

An explainable machine learning-driven proposal of pulmonary fibrosis biomarkers

“…In addition to introducing a new set of diagnostic genes able to classify IPF and healthy cases, this endeavor also attempts to bring into scientific attention several IPF-related features overlooked by previous in silico studies. For example, focusing on the genes of our lite model, apart from well-known pulmonary fibrosis players, such as MMP7 [46] , [47] , [48] , COL1A1 [47] , [49] , [50] , COL15A1 [47] , COMP [51] and AGER [52] , [53] , there are features that have not been extensively studied in pulmonary fibrosis. Although, interleukin 13 receptor subunit alpha 2 ( IL13RA2 ) has been evidenced to mediate pro-fibrotic TGFb-1 signaling in a colitis model [54] and was here correlated with several pulmonary function tests, its potential implication in pulmonary fibrosis needs to be thoroughly investigated.…”

Influence of the At-Arrival Host Transcriptome on Bovine Respiratory Disease Incidence during Backgrounding

“…Recently, Johnston and colleagues discovered that COL1A1 and COL1A2, the genes driving the aforementioned mechanisms, were the most down-regulated genes in whole blood collected from BRSV-challenged calves compared to sham-control calves [ 63 ]. While the exact mechanism of how these type-I collagen-associated genes relate to viral exposure and subsequent BRD development is unknown at this time, they are involved in airway macrophage-driven cell clearance, metalloproteinase regulation, and fibrogenesis [ 65 , 66 , 67 ]. Furthermore, platelet activity is linked to collagen exposure and is shown to increase both the adhesion capacity of lymphocytes and enhance T-cell differentiation [ 68 , 69 , 70 ].…”