title: Airborne lipid antigens mobilize resident intravascular NKT cells to induce allergic airway inflammation.
abstract: Airborne exposure to microbial cell wall lipids such as lipopolysaccharide triggers innate immune responses that regulate susceptibility to allergic airway inflammation. α-Glycosylceramides represent another widespread class of microbial lipids that directly stimulate innate-like, IL-4- and IL-13-producing, CD1d-restricted NKT cells. In this study, we demonstrate that NKT cells constitutively accumulate and reside in the microvasculature of the mouse lung. After a single airborne exposure to lipid antigen, they promptly extravasate to orchestrate the formation of peribronchiolar and interstitial lymphohistiocytic granulomas containing numerous eosinophils. Concomitant airborne exposure to ovalbumin (OVA) induces the priming of OVA-specific Th2 cells and IgE antibodies by the same dendritic cell coexpressing CD1d and MHC class II. Although NKT cell activation remains confined to the lipid-exposed lung and draining lymph nodes, Th2 cells recirculate and seed the lung of a parabiotic partner, conferring susceptibility to OVA challenge months after the initial exposure, in a manner independent of NKT cells and CD1d. Thus, transient recruitment and activation of lung-resident intravascular NKT cells can trigger long-term susceptibility to allergic airway inflammation.
authors.affiliation: Committee on Immunology, Department of Pathology, Howard Hughes Medical Institute; and 4 Section of Pulmonary and Critical Care Medicine, Department of Medicine; University of Chicago, Chicago, IL, USA.
authors.forename: Seth T
authors.initials: ST
authors.lastname: Scanlon
authors.forename: Seddon Y
authors.initials: SY
authors.lastname: Thomas
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Ferreira
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.forename: Thomas
authors.initials: T
authors.lastname: Krausz
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D055610:Antigens, CD1d / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005802:Genes, MHC Class II; D008055:Lipids / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*
chemical_list: D000941:Antigens; D055610:Antigens, CD1d; D018925:Chemokines; D008055:Lipids; D010047:Ovalbumin