Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of α-galactosylceramides

Karl O.A. Yu, Jin S. Im, Alberto Molano, Yves Dutronc, Petr A. Illanonov, Claire Forestier, Nagatoshi Fujiwara, Isa Arias, Sachiko Miyake, Takashi Yamamura, Young Tae Chang, Gurdyal S. Besra, Steven A. Porcelli

Research output: Contribution to journalArticle

271 Scopus citations

Abstract

A form of α-galactosylceramide, KRN7000, activates CD1d-restricted Vα14-invariant (Vα14i) natural killer (NK) T cells and initiates multiple downstream immune reactions. We report that substituting the C26:0 N-acyl chain of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of Vα14i NKT cell activation. One analogue containing a diunsaturated C20 fatty acid (C20:2) potently induced a T helper type 2-biased cytokine response, with diminished IFN-γ production and reduced Vα14i NKT cell expansion. C20:2 also exhibited less stringent requirements for loading onto CD1d than KRN7000, suggesting a mechanism for the immunomodulatory properties of this lipid. The differential cellular response elicited by this class of Vα14i NKT cell agonists may prove to be useful in immunotherapeutic applications.

Original languageEnglish (US)
Pages (from-to)3383-3388
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number9
DOIs
StatePublished - Mar 1 2005

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Keywords

  • Autoimmunity
  • Cytokines
  • Immunoregulation
  • Inflammation

ASJC Scopus subject areas

  • General

Cite this

Yu, K. O. A., Im, J. S., Molano, A., Dutronc, Y., Illanonov, P. A., Forestier, C., Fujiwara, N., Arias, I., Miyake, S., Yamamura, T., Chang, Y. T., Besra, G. S., & Porcelli, S. A. (2005). Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of α-galactosylceramides. Proceedings of the National Academy of Sciences of the United States of America, 102(9), 3383-3388. https://doi.org/10.1073/pnas.0407488102