α‐Galactosylceramide‐induced iNKT cells suppress experimental allergic asthma in sensitized mice: Role of IFN‐γ

Allergic asthma is a multifaceted syndrome consisting of eosinophil‐rich airway inflammation, bronchospasm, and airway hyper‐responsiveness (AHR). Using a mouse model of allergic asthma, we previously reported that invariant NKT (iNKT) cells increase the severity of this disease. Herein, we demonstr...

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Bibliographic Details
Published in:European Journal of Immunology 2005-10, Vol.35 (10), p.2793-2802
Main Authors: Hachem, Patricia, Lisbonne, Mariette, Michel, Marie‐Laure, Diem, Séverine, Roongapinun, Sukit, Lefort, Jean, Marchal, Gilles, Herbelin, André, Askenase, Philip W., Dy, Michel, Leite‐de‐Moraes, Maria C.
Format: Article
Language:English
Subjects:
Administration, Intranasal
Adoptive Transfer
Animals
Asthma
Asthma - immunology
Asthma - physiopathology
Asthma - prevention & control
Bronchial Hyperreactivity - immunology
Bronchial Hyperreactivity - prevention & control
Bronchoalveolar Lavage Fluid - chemistry
Bronchoalveolar Lavage Fluid - cytology
Bronchoalveolar Lavage Fluid - immunology
Cytokines - analysis
Cytokines - drug effects
Cytokines - immunology
Disease Models, Animal
Flow Cytometry
Galactosylceramides - administration & dosage
Hypersensitivity - immunology
Hypersensitivity - prevention & control
Hyper‐reactivity
Immunotherapy
Injections, Intravenous
Interferon-alpha - immunology
Killer Cells, Natural - drug effects
Killer Cells, Natural - immunology
Life Sciences
Male
Mice
NKT cells
Ovalbumin - immunology
Ovalbumin - pharmacology
α‐GalCer
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Summary:Allergic asthma is a multifaceted syndrome consisting of eosinophil‐rich airway inflammation, bronchospasm, and airway hyper‐responsiveness (AHR). Using a mouse model of allergic asthma, we previously reported that invariant NKT (iNKT) cells increase the severity of this disease. Herein, we demonstrate that a single i.v. injection of α‐galactosylceramide (α‐GalCer), 1 h before the first airway allergen challenge of OVA‐sensitized mice, abrogates elicitation of AHR, airway eosinophilia, IL‐4 and IL‐5 production in bronchoalveolar lavage fluid, and specific anti‐OVA IgE antibodies. Further, α‐GalCer administered intranasally also strongly inhibited the major symptoms of asthma in sensitized and challenged mice. α‐GalCer treatment induces iNKT cell accumulation in the lungs, and shifts their cytokine profile from pro‐asthmatic IL‐4 to a protective IFN‐γ production. The role of IFN‐γ from iNKT cells in protection was shown by adoptive transfer of sorted iNKT cells from OVA‐sensitized and α‐GalCer‐treated mice which protected immunized recipients from manifesting asthma by an IFN‐γ‐dependent pathway. Our findings demonstrate for the first time that α‐GalCer administered locally inhibits asthma symptoms, even in predisposed asthmatic mice, through an iNKT cell‐ and IFN‐γ‐dependent pathway. See accompanying commentary: http://dx.doi.org/10.1002/eji.200535425
ISSN:0014-2980
1521-4141
1365-2567
DOI:10.1002/eji.200535268