title: Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation.
abstract: Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborne allergen exposure. Determination of the factors that lead to the asthma phenotype in allergic individuals could guide treatment and identify novel therapeutic targets. We used segmental allergen challenge of allergic asthmatics (AA) and allergic nonasthmatic controls (AC) to determine whether there are differences in the airway immune response or airway structural cells that could drive the development of asthma. Both groups developed prominent allergic airway inflammation in response to allergen. However, asthmatic subjects had markedly higher levels of innate type 2 receptors on allergen-specific CD4+T cells recruited into the airway. There were also increased levels of type 2 cytokines, increased total mucin, and increased mucin MUC5AC in response to allergen in the airways of AA subjects. Furthermore, type 2 cytokine levels correlated with the mucin response in AA but not AC subjects, suggesting differences in the airway epithelial response to inflammation. Finally, AA subjects had increased airway smooth muscle mass at baseline measured in vivo using novel orientation-resolved optical coherence tomography. Our data demonstrate that the development of allergic asthma is dependent on the responsiveness of allergen-specific CD4+T cells to innate type 2 mediators as well as increased sensitivity of airway epithelial cells and smooth muscle to type 2 inflammation.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Josalyn L
authors.initials: JL
authors.lastname: Cho
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Morris F
authors.initials: MF
authors.lastname: Ling
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Adams
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Faustino
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Islam
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Roshi
authors.initials: R
authors.lastname: Afshar
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Griffith
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Harris
authors.affiliation: Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
authors.forename: Aylwin
authors.initials: A
authors.lastname: Ng
authors.affiliation: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Radicioni
authors.affiliation: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Amina A
authors.initials: AA
authors.lastname: Ford
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Andre K
authors.initials: AK
authors.lastname: Han
authors.affiliation: Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
authors.forename: Ramnik
authors.initials: R
authors.lastname: Xavier
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Kwok
authors.affiliation: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Boucher
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Moon
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Hamilos
authors.affiliation: Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kesimer
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Suter
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Medoff
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. aluster@mgh.harvard.edu.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000473:pathology; D016207:Cytokines; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D008168:Lung / Q000473:pathology; D009093:Mucus / Q000378:metabolism; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines