| First Author | Xia M | Year | 2018 |
| Journal | J Allergy Clin Immunol | Volume | 142 |
| Issue | 4 | Pages | 1243-1256.e17 |
| PubMed ID | 29627423 | Mgi Jnum | J:338502 |
| Mgi Id | MGI:6754842 | Doi | 10.1016/j.jaci.2018.03.009 |
| Citation | Xia M, et al. (2018) A Jagged 1-Notch 4 molecular switch mediates airway inflammation induced by ultrafine particles. J Allergy Clin Immunol 142(4):1243-1256.e17 |
| abstractText | BACKGROUND: Exposure to traffic-related particulate matter promotes asthma and allergic diseases. However, the precise cellular and molecular mechanisms by which particulate matter exposure acts to mediate these effects remain unclear. OBJECTIVE: We sought to elucidate the cellular targets and signaling pathways critical for augmentation of allergic airway inflammation induced by ambient ultrafine particles (UFP). METHODS: We used in vitro cell-culture assays with lung-derived antigen-presenting cells and allergen-specific T cells and in vivo mouse models of allergic airway inflammation with myeloid lineage-specific gene deletions, cellular reconstitution approaches, and antibody inhibition studies. RESULTS: We identified lung alveolar macrophages (AM) as the key cellular target of UFP in promoting airway inflammation. Aryl hydrocarbon receptor-dependent induction of Jagged 1 (Jag1) expression in AM was necessary and sufficient for augmentation of allergic airway inflammation by UFP. UFP promoted TH2 and TH17 cell differentiation of allergen-specific T cells in a Jag1- and Notch 4-dependent manner. Treatment of mice with an anti-Notch 4 antibody abrogated exacerbation of allergic airway inflammation induced by UFP. CONCLUSION: UFP exacerbate allergic airway inflammation by promoting a Jag1-Notch 4-dependent interaction between AM and allergen-specific T cells, leading to augmented TH cell differentiation. |
