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

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Abstract
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