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Bacterial CD1d-restricted glycolipids induce IL-10 production by human regulatory T cells upon cross-talk with invariant NKT cells

Koen Venken (UGent) , Tine Decruy (UGent) , SANDRINE ASPESLAGH (UGent) , Serge Van Calenbergh (UGent) , Bart Lambrecht (UGent) and Dirk Elewaut (UGent)
(2013) JOURNAL OF IMMUNOLOGY. 191(5). p.2174-2183
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Abstract
Invariant NKT (iNKT) cells and CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) are important immune regulatory T cells with Ag reactivity to glycolipids and peptides, respectively. However, the functional interplay between these cells in humans is poorly understood. We show that Tregs suppress iNKT cell proliferation induced by CD1d-restricted glycolipids, including bacterial-derived diacylglycerols, as well as by innate-like activation. Inhibition was related to the potency of iNKT agonists, making diacylglycerol iNKT responses very prone to suppression. Cytokine production by iNKT cells was differentially modulated by Tregs because IL-4 production was reduced more profoundly compared with IFN-gamma. A compelling observation was the significant production of IL-10 by Tregs after cell contact with iNKT cells, in particular in the presence of bacterial diacylglycerols. These iNKT-primed Tregs showed increased FOXP3 expression and superior suppressive function. Suppression of iNKT cell responses, but not conventional T cell responses, was IL-10 dependent, suggesting that there is a clear difference in mechanism between the Treg-mediated inhibition of these cell types. Our data highlight a physiologically relevant interaction between human iNKT and Tregs upon pathogen-derived glycolipid recognition that has a significant impact on the design of iNKT cell-based therapeutics.
Keywords
MEDIATED SUPPRESSION, MULTIPLE-SCLEROSIS, VIRAL-INFECTION, ACTIVATION, RESPONSES, ANTIGENS, DISEASE, RECOGNITION, INNATE, INFLAMMATION

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Citation

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Chicago
Venken, Koen, Tine Decruy, SANDRINE ASPESLAGH, Serge Van Calenbergh, Bart Lambrecht, and Dirk Elewaut. 2013. “Bacterial CD1d-restricted Glycolipids Induce IL-10 Production by Human Regulatory T Cells Upon Cross-talk with Invariant NKT Cells.” Journal of Immunology 191 (5): 2174–2183.
APA
Venken, K., Decruy, T., ASPESLAGH, S., Van Calenbergh, S., Lambrecht, B., & Elewaut, D. (2013). Bacterial CD1d-restricted glycolipids induce IL-10 production by human regulatory T cells upon cross-talk with invariant NKT cells. JOURNAL OF IMMUNOLOGY, 191(5), 2174–2183.
Vancouver
1.
Venken K, Decruy T, ASPESLAGH S, Van Calenbergh S, Lambrecht B, Elewaut D. Bacterial CD1d-restricted glycolipids induce IL-10 production by human regulatory T cells upon cross-talk with invariant NKT cells. JOURNAL OF IMMUNOLOGY. 2013;191(5):2174–83.
MLA
Venken, Koen, Tine Decruy, SANDRINE ASPESLAGH, et al. “Bacterial CD1d-restricted Glycolipids Induce IL-10 Production by Human Regulatory T Cells Upon Cross-talk with Invariant NKT Cells.” JOURNAL OF IMMUNOLOGY 191.5 (2013): 2174–2183. Print.
@article{4208258,
  abstract     = {Invariant NKT (iNKT) cells and CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) are important immune regulatory T cells with Ag reactivity to glycolipids and peptides, respectively. However, the functional interplay between these cells in humans is poorly understood. We show that Tregs suppress iNKT cell proliferation induced by CD1d-restricted glycolipids, including bacterial-derived diacylglycerols, as well as by innate-like activation. Inhibition was related to the potency of iNKT agonists, making diacylglycerol iNKT responses very prone to suppression. Cytokine production by iNKT cells was differentially modulated by Tregs because IL-4 production was reduced more profoundly compared with IFN-gamma. A compelling observation was the significant production of IL-10 by Tregs after cell contact with iNKT cells, in particular in the presence of bacterial diacylglycerols. These iNKT-primed Tregs showed increased FOXP3 expression and superior suppressive function. Suppression of iNKT cell responses, but not conventional T cell responses, was IL-10 dependent, suggesting that there is a clear difference in mechanism between the Treg-mediated inhibition of these cell types. Our data highlight a physiologically relevant interaction between human iNKT and Tregs upon pathogen-derived glycolipid recognition that has a significant impact on the design of iNKT cell-based therapeutics.},
  author       = {Venken, Koen and Decruy, Tine and ASPESLAGH, SANDRINE and Van Calenbergh, Serge and Lambrecht, Bart and Elewaut, Dirk},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  language     = {eng},
  number       = {5},
  pages        = {2174--2183},
  title        = {Bacterial CD1d-restricted glycolipids induce IL-10 production by human regulatory T cells upon cross-talk with invariant NKT cells},
  url          = {http://dx.doi.org/10.4049/jimmunol.1300562},
  volume       = {191},
  year         = {2013},
}

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