title: Pro- and Anti-Inflammatory Role of ChemR23 Signaling in Pollutant-Induced Inflammatory Lung Responses.
abstract: Inhalation of traffic-related particulate matter (e.g., diesel exhaust particles [DEPs]) is associated with acute inflammatory responses in the lung, and it promotes the development and aggravation of allergic airway diseases. We previously demonstrated that exposure to DEP was associated with increased recruitment and maturation of monocytes and conventional dendritic cells (DCs), resulting in TH2 polarization. Monocytes and immature DCs express the G-protein coupled receptor chemR23, which binds the chemoattractant chemerin. Using chemR23 knockout (KO) and corresponding wild-type (WT) mice, we determined the role of chemR23 signaling in response to acute exposure to DEPs and in response to DEP-enhanced house dust mite (HDM)-induced allergic airway inflammation. Exposure to DEP alone, as well as combined exposure to DEP plus HDM, elevated the levels of chemerin in the bronchoalveolar lavage fluid of WT mice. In response to acute exposure to DEPs, monocytes and monocyte-derived DCs accumulated in the lungs of WT mice, but this response was significantly attenuated in chemR23 KO mice. Concomitant exposure to DEP plus HDM resulted in allergic airway inflammation with increased eosinophilia, goblet cell metaplasia, and TH2 cytokine production in WT mice, which was further enhanced in chemR23 KO mice. In conclusion, we demonstrated an opposing role for chemR23 signaling depending on the context of DEP-induced inflammation. The chemR23 axis showed proinflammatory properties in a model of DEP-induced acute lung inflammation, in contrast to anti-inflammatory effects in a model of DEP-enhanced allergic airway inflammation.
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium; and sharen.provoost@UGent.be.
authors.forename: Sharen
authors.initials: S
authors.lastname: Provoost
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium; and.
authors.forename: Katrien C
authors.initials: KC
authors.lastname: De Grove
authors.affiliation: Euroscreen S.A., 6041 Gosselies, Belgium.
authors.forename: Graeme L
authors.initials: GL
authors.lastname: Fraser
authors.affiliation: Euroscreen S.A., 6041 Gosselies, Belgium.
authors.forename: Vincent J
authors.identifier: http://orcid.org/0000-0002-5877-6683
authors.initials: VJ
authors.lastname: Lannoy
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium; and.
authors.forename: Kurt G
authors.identifier: http://orcid.org/0000-0003-4943-3782
authors.initials: KG
authors.lastname: Tournoy
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium; and.
authors.forename: Guy G
authors.initials: GG
authors.lastname: Brusselle
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium; and.
authors.forename: Tania
authors.initials: T
authors.lastname: Maes
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium; and.
authors.forename: Guy F
authors.initials: GF
authors.lastname: Joos
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052638:Particulate Matter / Q000633:toxicity; D011014:Pneumonia / Q000209:etiology / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D001335:Vehicle Emissions / Q000633:toxicity
chemical_list: C486456:CMKLR1 protein, mouse; D052638:Particulate Matter; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D001335:Vehicle Emissions