LAUSR

&NA; Urban particulate matter (UPM) air pollution and vitamin D deficiency are detrimentally associated with respiratory health. This is hypothesized to be due in part to regulation of IL‐17A, which UPM is reported to promote. Here, we used a myeloid dendritic cell (DC)‐memory CD4+ T cell co‐culture system to characterize UPM‐driven IL‐17A+ cells, investigate the mechanism by which UPM‐primed DCs promote this phenotype, and address evidence for cross‐regulation by vitamin D. CD1c+ myeloid DCs were cultured overnight with or without a reference source of UPM and/or active vitamin D (1,25[OH]2D3) before they were co‐cultured with autologous memory CD4+ T cells. Supernatants were harvested for cytokine analysis on Day 5 of co‐culture, and intracellular cytokine staining was performed on Day 7. UPM‐primed DCs increased the proportion of memory CD4+ T cells expressing the T helper 17 cell (Th17)‐associated cytokines IL‐17A, IL‐17F, and IL‐22, as well as IFN‐&ggr;, granulocyte‐macrophage colony‐stimulating factor, and granzyme B. Notably, a large proportion of the UPM‐driven IL‐17A+ cells co‐expressed these cytokines, but not IL‐10, indicative of a proinflammatory Th17 profile. UPM‐treated DCs expressed elevated levels of il23 mRNA and increased secretion of IL‐23p40. Neutralization of IL‐23 in culture reduced the frequency of IL‐17A+IFN‐&ggr;+ cells without affecting cell proliferation. 1,25(OH)2D3 counteracted the UPM‐driven DC maturation and inhibited the frequency of IL‐17A+IFN‐&ggr;+ cells, most prominently when DCs were co‐treated with the corticosteroid dexamethasone, while maintaining antiinflammatory IL‐10 synthesis. These data indicate that UPM might promote an inflammatory milieu in part by inducing an IL‐23‐driven proinflammatory Th17 response. Restoring vitamin D sufficiency may counteract these UPM‐driven effects without obliterating important homeostatic immune functions.