PM 10 Impairs CD56 dim NK Cell Cytotoxicity via FNBP1 Suppression to Exacerbate Rheumatoid Arthritis: Insights from Multimodal Multi‐Omics

Air pollution (AP), intensified by industrialization and urbanization, is a key environmental factor linked to rheumatoid arthritis (RA). However, its molecular and immunological impact on RA remains unclear. This study integrates epidemiological data, bioinformatics, single-cell transcriptomics, and animal models to investigate how AP contributes to the development of RA. Global epidemiological analysis shows rising RA prevalence in over 95% of countries. Mendelian randomization analysis indicated a positive correlation between PM₁₀ exposure and the risk of RA. Machine learning identifies Formin Binding Protein 1 (FNBP1) as a key air pollution-related gene (APRG), with decreasing expression in RA patients and strong correlation with disease activity. PM₁₀ exposure may impair natural killer (NK) cell differentiation and cytotoxicity by suppressing FNBP1 expression, ultimately weakening immune surveillance and exacerbating inflammatory responses. Furthermore, by integrating single-cell sequencing, animal models, and human-derived cell experiments, we demonstrated that PM₁₀ exposure aggravates inflammation and joint damage in a collagen-induced arthritis (CIA) model. Mechanistically, PM₁₀ likely impairs the cytotoxic function of CD56^dim NK cells through the modulation of FNBP1. Taken together, our research results have unveiled a completely novel mechanistic hypothesis regarding the onset and development of RA, the "PM₁₀-FNBP1-NK cells" axis.