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Published ahead of print on March 31, 2005, doi:10.1165/rcmb.2004-0010OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 33, pp. 22-31, 2005
© 2005 American Thoracic Society
DOI: 10.1165/rcmb.2004-0010OC

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

Hiroyuki Matsuda, Takafumi Suda, Jun Sato, Toshi Nagata, Yukio Koide, Kingo Chida and Hirotoshi Nakamura

Second Division, Department of Internal Medicine, and Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Hamamatsu, Japan

Correspondence and requests for reprints should be addressed to Takafumi Suda, M.D., Ph.D., Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192 Japan. E-mail: suda{at}hama-med.ac.jp

{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.

Key Words: asthma • natural killer T cell • {alpha}-galactosylceramide • interferon-{gamma}




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