Alpha-galactosylceramide-induced iNKT cells suppress experimental allergic asthma in sensitized mice: role of IFN-gamma.
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 alpha-galactosylceramide (alpha-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, alpha-GalCer administered intranasally also strongly inhibited the major symptoms of asthma in sensitized and challenged mice. Alpha-GalCer treatment induces iNKT cell accumulation in the lungs, and shifts their cytokine profile from pro-asthmatic IL-4 to a protective IFN-gamma production. The role of IFN-gamma from iNKT cells in protection was shown by adoptive transfer of sorted iNKT cells from OVA-sensitized and alpha-GalCer-treated mice which protected immunized recipients from manifesting asthma by an IFN-gamma-dependent pathway. Our findings demonstrate for the first time that alpha-GalCer administered locally inhibits asthma symptoms, even in predisposed asthmatic mice, through an iNKT cell- and IFN-gamma-dependent pathway.
Hachem
Patricia
P
Centre National de la Recherche Scientifique-Unité Mixte de Recherche 8147, Paris V, Hôpital Necker, Paris, France.
Lisbonne
Mariette
M
Michel
Marie-Laure
ML
Diem
Séverine
S
Roongapinun
Sukit
S
Lefort
Jean
J
Marchal
Gilles
G
Herbelin
André
A
Askenase
Philip W
PW
Dy
Michel
M
Leite-de-Moraes
Maria C
MC
D000281:Administration, Intranasal; D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000008:administration & dosage*; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007275:Injections, Intravenous; D016898:Interferon-alpha / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology
D016207:Cytokines; D005699:Galactosylceramides; D016898:Interferon-alpha; C493154:alpha-galactosylceramide; D010047:Ovalbumin