Shared and Stage-Dependent Myeloid Transcriptional Signatures in Pulmonary Fibrosis Progression

An increase in circulating monocytes is associated with worse progression and increased mortality in idiopathic pulmonary fibrosis (IPF), and the appearance and progression of interstitial lung abnormalities (ILA), representing an early stage of pulmonary fibrosis. To explore the role of monocytes in disease initiation and progression, we analyzed scRNA-seq data from peripheral blood mononuclear cells (PBMCs) from control, ILA, and IPF samples (n=15, 9, 24, respectively), Differential expression revealed 6,395 genes that were significantly altered between the control and IPF groups, and 7,578 between the ILA and IPF groups. 5,021 genes were commonly dysregulated in both comparisons, with consistent directionality of change, indicating convergent transcriptional reprogramming during disease progression. Gene Ontology enrichment of commonly downregulated genes identified processes central to immune regulation, including Toll-like receptor 8 signaling, leukocyte migration in immune response, and immune complex clearance (fold enrichment 7.36, FDR ~0.05). In contrast, commonly upregulated genes were enriched in stress- and remodeling-related pathways, including regulation of leukocyte adhesion to endothelial cells, and T-helper 1 cell activation (fold enrichment up to 8.96, FDR