Journal article
Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation
Science translational medicine, Vol.8(359), pp.359ra132-359ra132
10/05/2016
DOI: 10.1126/scitranslmed.aag1370
PMCID: PMC5399547
PMID: 27708065
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.
Details
- Title: Subtitle
- Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation
- Creators
- Josalyn L Cho - 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, USAMorris F Ling - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USADavid C Adams - Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USALucas Faustino - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USASabina A Islam - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USARoshi Afshar - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAJason W Griffith - 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, USARobert S Harris - Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAAylwin Ng - 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, USAGiorgia Radicioni - Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAAmina A Ford - Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAAndre K Han - 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, USARamnik Xavier - 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, USAWilliam W Kwok - Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USARichard Boucher - Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAJames J Moon - 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, USADaniel L Hamilos - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAMehmet Kesimer - Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAMelissa J Suter - Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USABenjamin D Medoff - 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, USAAndrew D Luster - 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
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.8(359), pp.359ra132-359ra132
- DOI
- 10.1126/scitranslmed.aag1370
- PMID
- 27708065
- PMCID
- PMC5399547
- NLM abbreviation
- Sci Transl Med
- ISSN
- 1946-6234
- eISSN
- 1946-6242
- Grant note
- R01 HL110906 / NHLBI NIH HHS U19 AI095261 / NIAID NIH HHS R37 AI040618 / NIAID NIH HHS R01 HL103940 / NHLBI NIH HHS R01 CA167827 / NCI NIH HHS P30 DK043351 / NIDDK NIH HHS
- Language
- English
- Date published
- 10/05/2016
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094539202771
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