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Published ahead of print on March 31, 2005, doi:10.1165/rcmb.2004-0010OC

Am. J. Respir. Cell Mol. Biol., Volume 33, Number 1, July 2005, 22-31

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Submitted on January 11, 2004
Revised on March 31, 2005

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

Hiroyuki Matsuda1, Takafumi Suda1*, Jun Sato1, Toshi Nagata2, Yukio Koide2, Kingo Chida1, and Hirotoshi Nakamura1

1 Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan, 2 Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Hamamatsu, Japan

* To whom correspondence should be addressed. 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 (BAL). This inhibition of allergic inflammation was associated with a significant decrease in the levels of IL-4, IL-5, and IL-13 in BAL fluid and in the number of goblet cells. Additionally, this ligand significantly inhibited airway hyperresponsiveness to inhaled methacholine and raised the serum levels of ovalbumin (OVA)-specific IgG2a with a decrease in those of OVA-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.




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