The natural killer T-cell ligand α-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice

Seokmann Hong, Michael T. Wilson, Isao Serizawa, Lan Wu, Nagendra Singh, Olga V. Naidenko, Toru Miura, Tomoku Haba, David C. Scherer, Jie Wei, Mitchell Kronenberg, Yasuhiko Koezuka, Luc Van Kaer

Research output: Contribution to journalArticle

502 Scopus citations

Abstract

Diabetes in non-obese diabetic (NOD) mice is mediated by pathogenic T-helper type 1 (Th1) cells that arise because of a deficiency in regulatory or suppressor T cells. Vα14-Jα15 natural killer T (NKT) cells recognize lipid antigens presented by the major histocompatibility complex class I-like protein CD1d (refs. 3, 4). We have previously shown that in vivo activation of Vα14 NKT cells by α-galactosylceramide (α-GalCer) and CD1d potentiates Th2-mediated adaptive immune responses. Here we show that α-GalCer prevents development of diabetes in wild-type but not CD1d-deficient NOD mice. Disease prevention correlated with the ability of αGalCer to suppress interferon-γ but not interleukin-4 production by NKT cells, to increase serum immunoglobulin E levels, and to promote the generation of islet autoantigen-specific Th2 cells. Because α-GalCer recognition by NKT cells is conserved among mice and humans, these findings indicate that α-GalCer might be useful for therapeutic intervention in human diseases characterized by Th1-mediated pathology such as Type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)1052-1056
Number of pages5
JournalNature Medicine
Volume7
Issue number9
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hong, S., Wilson, M. T., Serizawa, I., Wu, L., Singh, N., Naidenko, O. V., Miura, T., Haba, T., Scherer, D. C., Wei, J., Kronenberg, M., Koezuka, Y., & Van Kaer, L. (2001). The natural killer T-cell ligand α-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice. Nature Medicine, 7(9), 1052-1056. https://doi.org/10.1038/nm0901-1052