Publication date: Available online 5 April 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Mingcan Xia, Hani Harb, Arian Saffari, Constantinos Sioutas, Talal A. Chatila
BackgroundExposure to traffic-related particulate matter (PM) promotes asthma and allergic diseases. However, the precise cellular and molecular mechanisms by which PM exposure acts to mediate these effects remain unclear.ObjectiveWe sought to elucidate the cellular targets and signaling pathways critical for the augmentation of allergic airway inflammation induced by ambient ultra fine particles (UFP).MethodsWe employed in vitro cell culture assays using lung-derived antigen presenting cells and allergen-specific T cells, and in vivo mouse models of allergic airway inflammation that employed myeloid lineage-specific gene deletions, cellular reconstitution approaches and antibody inhibition studies.ResultsWe identified lung alveolar macrophage (AM) as the key cellular target of UFP in promoting airway inflammation. Aryl hydrocarbon receptor (AhR)-dependent induction of Jagged 1 (Jag1) expression in AM was necessary and sufficient for the augmentation of allergic airway inflammation by UFP. UFP promoted Th2 and Th17 cell differentiation of allergen-specific T cells in a Jag1- and Notch4-dependent manner. Treatment of mice with an anti-Notch 4 antibody abrogated the exacerbation of allergic airway inflammation induced by UFP.ConclusionUFP exacerbate allergic airway inflammation by promoting a Jag1-Notch4-dependent interaction between Alveolar Macrophages and Allergen-Specific T cells, leading to augmented Th cell differentiation.
Graphical abstract
Teaser
Traffic related particulate matter induce the expression of Jagged1 on alveolar macrophages in an aryl hydrocabron receptor-dependent manner, which in turn interacts with Notch4 on Allergen-Specific T cells to promote allergic airway inflammation.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2HcKID9
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