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

doi:10.1073/pnas.0407488102

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

Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

303 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 language	English (US)
Pages (from-to)	3383-3388
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	9
DOIs	https://doi.org/10.1073/pnas.0407488102
State	Published - Mar 1 2005

Keywords

Autoimmunity
Cytokines
Immunoregulation
Inflammation

ASJC Scopus subject areas

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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

Yu, KOA, Im, JS, Molano, A, Dutronc, Y, Illanonov, PA, Forestier, C, Fujiwara, N, Arias, I, Miyake, S, Yamamura, T, Chang, YT, Besra, GS & Porcelli, SA 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, vol. 102, no. 9, pp. 3383-3388. https://doi.org/10.1073/pnas.0407488102

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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.",

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AU - Dutronc, Yves

AU - Illanonov, Petr A.

AU - Forestier, Claire

AU - Fujiwara, Nagatoshi

AU - Arias, Isa

AU - Miyake, Sachiko

AU - Yamamura, Takashi

AU - Chang, Young Tae

AU - Besra, Gurdyal S.

AU - Porcelli, Steven A.

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N2 - 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.

AB - 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.

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

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