Exposure to ambient air pollution (AAP) has been associated with exacerbation of asthma, the immune mechanism of which, however, is largely unknown. METHODS: In a cohort of 49 subjects, using single-cell mass cytometry, we characterized and compared immune network changes in peripheral blood mononuclear cells associated with long-term exposure to AAP, asthma, and both, and estimated contributions to these changes from individual air pollutants, measured by a spatial-temporal regression model. RESULTS: Asthma with but not without long-term exposure to AAP is associated with increased proinflammatory CD16 + monocytes and IL-4 production of CD4 + T cells, and decreased B cells and IL-4 and IL-17A production of CD8 + T cells. Tetanus-specific IgG was significantly reduced in subjects with long-term exposure to AAP (p50.02). Seven individual pollutants (O 3 , EC, NO, NO 2 , PM 10 , PM 2.5 , PAH), each correlated with specific sets of immune changes but also shared a common set of changes over short-term (< _6mons) and long-term (>6mons) exposure, including increased na€ ıve T cells, IL-4 production of T cells, and decreased memory T cells. PM 2.5 and NO 2 associated with more immune changes than other pollutants during short-term and long-term exposure, respectively. CONCLUSIONS: Linking single-cell immune profiling with AAP exposure monitoring, we revealed a remodeling of the immune system in asthmatics with long-term exposure to AAP, which is associated with promoted inflammatory monocytes, suppressed type 2 phenotypes of CD8 + T cells, and diminished immunity. We also revealed contributions of individual pollutants to immune network. These results point to new mechanisms and potential new targets for AAP-associated asthma.