Background Traffic-related particulate matter (PM) has been linked to heightened incidence of asthma and allergic diseases. However, molecular mechanisms by which PM exposure promote allergic diseases remain elusive. Objective We sought to determine the expression, function and regulation of pathways involved in the promotion by PM of allergic airway inflammation. Methods We employed gene expression transcriptional profiling, in vitro culture assays, and vivo murine models of allergic airway inflammation. Results We identified genes of the Notch pathway, most notably Jagged 1 (Jag1), as targets of PM induction in human monocytes and murine dendritic cells (DCs). PM, especially ultrafine particles (UFP), upregulated T helper cytokine, IgE production and allergic airway inflammation in mice in a Jag1 and Notch-dependent manner especially in the context of the pro-asthmatic IL-4 receptor allele Il4raR576. PM-induced Jag1 expression was mediated by the aryl hydrocarbon receptor (AhR), which bound to and activated AhR response elements in the Jag1 promoter. Pharmacological antagonism of AhR or its lineage-specific deletion in CD11c+ cells abrogated the augmentation of airway inflammation by PM. Conclusion PM activate an AhR-Jag1-Notch cascade to promote allergic airway inflammation in concert with pro-asthmatic alleles.

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