Ozone Exposure Induces Anemia via Immune-Inflammatory Disruption of Erythroid Homeostasis

Ground-level ozone (O₃), a major ambient air pollutant, is epidemiologically linked to anemia, but its mechanisms remain unclear. This study employed integrated phenotypic, histopathological, and transcriptomic analyses to explore the molecular mechanisms of O₃-induced anemia. Male C57BL/6J mice underwent 28-day whole-body O₃ exposure at environmentally relevant concentrations (0.25 and 0.50 ppm, 4 h/day) alongside clean air controls. Significant hematological alterations occurred only at 0.50 ppm, including reduced erythroid parameters (red blood cells, hemoglobin, hematocrit, and reticulocytes) and systemic immune-inflammatory activation (increased lymphocyte count). This exposure level induced hematopoietic damage manifested as impaired progenitor cell differentiation (CFU-GEMM colony-forming capacity decreased by 20.55%, <i>p</i> < 0.05), reduced bone marrow hematopoietic cells, and extramedullary hematopoiesis in the spleen. Transcriptomic analysis identified 30 immune-inflammatory-related differentially expressed genes (IR-DEGs). Hierarchical network analysis integrating protein-protein interaction topology and transcriptional regulation revealed a core regulatory axis of transcription factors and 7 hub genes. Quantitative real-time PCR (qRT-PCR) and protein assays demonstrated that <i>Jund</i> is one of the key nodes in the regulatory network, which regulates critical immune-inflammatory genes (Ccl5, Lck, and Ifng). These findings indicate that <i>Jund</i>, as a key transcription factor in immune-inflammatory processes, mediates O₃-induced disruption of erythrocyte homeostasis, thereby providing experimental evidence for environmental anemia prevention.