Nitrogen dioxide exposure promotes CD8+T cell infiltration and contributes to increased susceptibility to ulcerative colitis: An integrative multi‑omics, artificial intelligence, and mouse model study.

The global incidence of ulcerative colitis (UC) has significantly increased in rapidly industrializing nations, with numerous studies highlighting environmental exposures, particularly nitrogen dioxide (NO2), as potential contributors to disease susceptibility. However, the clinical implications and molecular mechanisms linking NO2 exposure to UC susceptibility remain poorly understood. This study investigated the associations between NO2 and UC by integrating multi-omics data. We identified a CD8+ T cell subpopulation with a distinct phenotype characterized by perforin production, which potentially exacerbated colonic inflammation related to NO2 exposure. To validate this hypothesis, we established mouse models exposed to NO2, confirming increased CD8+ T cell infiltration and elevated perforin secretion through immunofluorescent (IF) staining. Employing artificial intelligence techniques, we identified Cell Division Cycle 25B (CDC25B) as a gene of interest correlated with putative NO2-related UC signatures. Finally, through molecular docking (MD) and molecular dynamics simulations (MDS), we identified ozanimod as one of several computationally nominated compounds associated with the CDC25B‑related network; however, none of these computational predictions were experimentally validated in the present study. Collectively, these findings suggest a correlative link between perforin or CD8+ T cell-associated colonic inflammation and NO2-associated UC susceptibility, and nominate CDC25B as a candidate gene for further investigation.