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Modulation of CD1d-restricted NKT cell responses by using N- acyl variants of α-galactosylceramides
Open accessAbstract
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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Saposin C is required for lipid presentation by human CD1b
Winau, F., Schwierzeck, V., Hurwitz, R., Remmel, N., Sieling, P. A., Modlin, R. L., Porcelli, S. A., Brinkmann, V., Sugita, M., Sandhoff, K., et al. (2004) · Nature Immunology · doi:10.1038/ni1035 · Cited by 168
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Cited by
Targeting natural killer cells and natural killer T cells in cancer
Vivier, E., Ugolini, S., Blaise, D., Chabannon, C., & Brossay, L. (2012) · Nature Reviews Immunology · doi:10.1038/nri3174 · Cited by 850
Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions
Brennan, P. J., Brigl, M., & Brenner, M. B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3369 · Cited by 835
Sphingolipid and Glycosphingolipid Metabolic Pathways in the Era of Sphingolipidomics
Merrill, A. H. (2011) · Chemical Reviews · doi:10.1021/cr2002917 · Cited by 785
Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria
Kinjo, Y., Tupin, E., Wu, D., Fujio, M., Garcia-Navarro, R., Benhnia, M. R.-E.-I., Zajonc, D. M., Ben-Menachem, G., Ainge, G. D., Painter, G. F., et al. (2006) · Nature Immunology · doi:10.1038/ni1380 · Cited by 640
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531
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Metadata
- Authors
- Yu, K. O. A., Im, J. S., Molano, A., Dutronc, Y., Illarionov, P. A., Forestier, C., Fujiwara, N., Arias, I., Miyake, S., Yamamura, T., Chang, Y.-T., Besra, G. S., & Porcelli, S. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-02-18
- Volume
- 102
- Issue
- 9
- Pages
- 3383-3388
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2142656879
- Cited by
- 337
- References
- 1
- FWCI
- 9.34
- Type
- journal article
- Language
- en
- Open access
- green
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- Yu, K. O. A., Im, J. S., Molano, A., Dutronc, Y., Illarionov, 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. https://doi.org/10.1073/pnas.0407488102
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