Single-Cell RNA Analysis Reveals Aberrant Expression of Immune-Related Genes and Transcriptional Regulation of NK Cells in Chronic Obstructive Pulmonary Disease

An increase in the number of natural killer (NK) cells in the lungs can be observed in chronic obstructive pulmonary disease (COPD). Immune-related genes (IRGs) play a crucial role in the differentiation of NK cells; however, the expression of IRGs and the possible regulatory mechanisms involved in COPD remain unclear. Single-cell RNA sequencing (scRNA seq) data of lung tissue of COPD patients were analyzed to screen NK cell cluster marker genes obtained in the ImmPort database. IRG activity in NK cell differential genes was calculated using the AUCell package. Analysis of batch sequencing datasets of biopsy tissue under COPD bronchoscopy to explore common IRGs in patients with COPD was conducted. Relevant regulatory transcription factors (TFs) were identified from the human TFDB data-base. Protein-protein interaction (PPI) networks for key TFs were generated by STRING database. A total of 12 different cell types were identified, among which the number of NK cells in COPD patients increased significantly. Gene-set enrichment analysis showed that immune response pathway was significantly enriched based on differentially expressed genes (DEGs) in NK cells. We found 55 co-expressed common IRGs and 43 co-expressed TFs in scRNA sequencing data and bulk RNA sequencing data. The PPI network indicates that EGR1, JUN, and FOS are hub TFs. In conclusion, we suggest that NK cells may be involved in chronic airway inflammation in COPD patients through bioinformatics analysis of scRNA and bulk RNA sequencing data. Specifically, EGR1 may participate in the transcriptional regulation of IRGs in NK cells, with potential involvement of calcium signaling and TGF-β/Smad pathways.