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

Pediatrics

University at Buffalo

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

315 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
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

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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

@article{de68d09ae78c4615860bf784d5e73b0d,

title = "Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of α-galactosylceramides",

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.",

keywords = "Autoimmunity, Cytokines, Immunoregulation, Inflammation",

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

year = "2005",

month = mar,

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doi = "10.1073/pnas.0407488102",

language = "English",

volume = "102",

pages = "3383--3388",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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number = "9",

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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

TY - JOUR

T1 - Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of α-galactosylceramides

AU - Yu, Karl O.A.

AU - Im, Jin S.

AU - Molano, Alberto

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.

PY - 2005/3/1

Y1 - 2005/3/1

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.

KW - Autoimmunity

KW - Cytokines

KW - Immunoregulation

KW - Inflammation

UR - https://www.scopus.com/pages/publications/20044387608

U2 - 10.1073/pnas.0407488102

DO - 10.1073/pnas.0407488102

M3 - Article

C2 - 15722411

SN - 0027-8424

VL - 102

SP - 3383

EP - 3388

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 9

ER -

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

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Keywords

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