alpha-Galactosylceramide, a ligand of natural killer T cells, inhibits allergic airway inflammation.
alpha-Galactosylceramide (alpha-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)-gamma and interleukin (IL)-4. However, it has not been determined whether alpha-GalCer-activated NKT cells modulate allergic inflammation. Because alpha-GalCer induces a large amount of IFN-gamma production by NKT cells, we hypothesized that an in vivo administration of alpha-GalCer could inhibit allergic airway inflammation in mice. Strikingly, a single intraperitoneal injection of alpha-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 IFN-gamma knockout mice, however, alpha-GalCer failed to exert such inhibitory effects in this asthma model. These results indicate that alpha-GalCer prevents allergic airway inflammation possibly through IFN-gamma production by ligand-activated NKT cells, suggesting the potential therapeutic application of alpha-GalCer in asthma.
Matsuda
Hiroyuki
H
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.
Suda
Takafumi
T
Sato
Jun
J
Nagata
Toshi
T
Koide
Yukio
Y
Chida
Kingo
K
Nakamura
Hirotoshi
H
D000818:Animals; D000941:Antigens / Q000737:chemistry; D001249:Asthma / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005699:Galactosylceramides / Q000502:physiology*; D020397:Goblet Cells / Q000473:pathology*; D006965:Hyperplasia; D006967:Hypersensitivity; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology*; D008024:Ligands; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D018418:Th2 Cells; D013997:Time Factors
D000941:Antigens; D005699:Galactosylceramides; D007074:Immunoglobulin G; D008024:Ligands; C493154:alpha-galactosylceramide; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin