-Galactosylceramide, a Ligand of Natural Killer T Cells, Inhibits Allergic Airway Inflammation

-Galactosylceramide ( -GalCer) is a specific ligand of natural killer T cells (NKT cells) that regulates the immune responses such as tumor rejection and autoimmunity by producing interferon (IFN)and interleukin (IL)-4. However, it has not been determined whether -GalCer–activated NKT cells modulate allergic inflammation. Because -GalCer induces a large amount of IFNproduction by NKT cells, we hypothesized that an in vivo administration of -GalCer could inhibit allergic airway inflammation in mice. Strikingly, a single intraperitoneal injection of -GalCer almost completely abrogated an infiltrate with eosinophils in the lung tissue as well as in the bronchoalveolar lavage. This inhibition of allergic inflammation was associated with a significant decrease in the levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and in the number of goblet cells. In addition, this ligand significantly inhibited airway hyperresponsiveness to inhaled methacholine and raised the serum levels of ovalbumin-specific IgG2a with a decrease in those of ovalbumin-specific IgE. In IFNknockout mice, however, -GalCer failed to exert such inhibitory effects in this asthma model. These results indicate that -GalCer prevents allergic airway inflammation possibly through IFNproduction by ligand-activated NKT cells, suggesting the potential therapeutic application of -GalCer in asthma.