Different Transcriptome Features of Peripheral Blood Mononuclear Cells in Non-Emphysematous Chronic Obstructive Pulmonary Disease

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Abstract
Non-emphysematous chronic obstructive pulmonary disease (COPD), which is defined based on chest computed tomography findings, presented different transcriptome features of peripheral blood mononuclear cells (PBMCs) compared with emphysematous COPD. Enrichment analysis of transcriptomic data in COPD demonstrated that the “Hematopoietic cell lineage” pathway in Kyoto Encyclopedia of Genes and Genomes pathway analysis was highly upregulated, suggesting that cellular dynamic dysregulation in COPD lungs is affected by pathologically modified PBMCs. The differentially expressed genes (DEGs) upregulated in PBMCs reflected the disease state of non-emphysematous COPD. Upregulated DEGs such as XCL1, PRKCZ, TMEM102, CD200R1, and AQP1 activate T lymphocytes and eosinophils. Upregulating keratan sulfate biosynthesis and metabolic processes is associated with protection against the destruction of the distal airways. ITGA3 upregulation augments interactions with extracellular matrix proteins, and COL6A1 augments the profibrotic mast cell phenotype during alveolar collagen VI deposition. Upregulating HSPG2, PDGFRB, and PAK4 contributes to the thickening of the airway wall, and upregulating SERPINF1 expression explains the better-preserved vascular bed. Therefore, gene expression and pathway analysis in PBMCs in patients with non-emphysematous COPD represented type 2 immune responses and airway remodeling features. Therefore, these patients have asthmatic potential despite no clinical signs of asthma, in contrast to those with emphysematous COPD.
Funding Information
  • JSPS KAKENHI (19K17663, 22K16163, 22H03076, JP21gm1210003, 223fa627003h0001, 20FC1027, 23FC1031)
  • AMED-CREST (19K17663, 22K16163, 22H03076, JP21gm1210003, 223fa627003h0001, 20FC1027, 23FC1031)
  • Japan Agency for Medical Research and Development (19K17663, 22K16163, 22H03076, JP21gm1210003, 223fa627003h0001, 20FC1027, 23FC1031)
  • Intractable Respiratory Diseases and Pulmonary Hypertension Research Group, Ministry of Health, Labor and Welfare, Japan (19K17663, 22K16163, 22H03076, JP21gm1210003, 223fa627003h0001, 20FC1027, 23FC1031)

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