PM2.5 Induces Cell-Specific Transcriptomic Alterations in the Lungs of Juvenile Mice.

INTRODUCTION: Fine particulate matter (PM(2.5)) is a major environmental pollutant associated with significant respiratory morbidity in children. However, its cell-type-specific effects on the lungs and the underlying molecular mechanisms remain poorly defined. METHODS: This study established a juvenile mouse model of PM(2.5) airway exposure to assess transcriptional alterations in lung cells via single-cell RNA sequencing (scRNA-seq). Differentially expressed genes were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Lung histopathology was evaluated through hematoxylin and eosin staining. RESULTS: Histological staining indicated that PM(2.5) inhalation induces structural damage in the lung tissue. ScRNA-seq analysis revealed that macrophages, dendritic cells (DCs), lymphocytes, epithelial cells, and stromal cells in the lungs of juvenile mice exhibited the most prominent differential gene expression following PM(2.5) instillation, whereas B cells and endothelial cells showed the least. In particular, GO and KEGG analyses indicated that alveolar macrophages exhibited significant upregulation of oxidative phosphorylation (OXPHOS) pathways and downregulation of antibacterial defense mechanisms. CD209(+) DCs showed suppressed antigen presentation and altered energy metabolism, primarily via enhanced OXPHOS. Lymphocytes, including NK and CD4(+) T cells, displayed modest dysregulation in ribosomal activity. Among non-immune cells, ciliated cells activated interferon signaling, while adventitial fibroblasts showed increased ribosomal protein translation and calcium ion channel regulation. PM(2.5) exposure also reshaped cell-cell communication networks, particularly involving alveolar macrophages and immune cells. CONCLUSION: These findings reveal cell-type-specific transcriptomic responses to PM(2.5) in juvenile lungs, emphasizing its potential to disrupt immune homeostasis and contribute to pulmonary disease development in children.