| First Author | Xia M | Year | 2015 |
| Journal | J Allergy Clin Immunol | Volume | 136 |
| Issue | 2 | Pages | 441-53 |
| PubMed ID | 25825216 | Mgi Jnum | J:321319 |
| Mgi Id | MGI:6819282 | Doi | 10.1016/j.jaci.2015.02.014 |
| Citation | Xia M, et al. (2015) Vehicular exhaust particles promote allergic airway inflammation through an aryl hydrocarbon receptor-notch signaling cascade. J Allergy Clin Immunol 136(2):441-53 |
| abstractText | BACKGROUND: Traffic-related particulate matter (PM) has been linked to a heightened incidence of asthma and allergic diseases. However, the molecular mechanisms by which PM exposure promotes allergic diseases remain elusive. OBJECTIVE: We sought to determine the expression, function, and regulation of pathways involved in promotion of allergic airway inflammation by PM. METHODS: We used gene expression transcriptional profiling, in vitro culture assays, and in vivo murine models of allergic airway inflammation. RESULTS: We identified components of the Notch pathway, most notably Jagged 1 (Jag1), as targets of PM induction in human monocytes and murine dendritic cells. PM, especially ultrafine particles, upregulated TH cytokine levels, IgE production, and allergic airway inflammation in mice in a Jag1- and Notch-dependent manner, especially in the context of the proasthmatic 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. Pharmacologic antagonism of AhR or its lineage-specific deletion in CD11c(+) cells abrogated the augmentation of airway inflammation by PM. CONCLUSION: PM activates an AhR-Jag1-Notch cascade to promote allergic airway inflammation in concert with proasthmatic alleles. |
