- Author
- Victor Bosteels (UGent) , Sandra Maréchal (UGent) , Clint De Nolf (UGent) , Sofie Rennen (UGent) , Jonathan Maelfait (UGent) , Simon Tavernier (UGent) , Jessica Vetters (UGent) , Evelien Van De Velde (UGent) , Farzaneh Fayazpour (UGent) , Kim Deswarte (UGent) , Alexander Lamoot, Julie Van Duyse (UGent) , Liesbet Martens (UGent) , Cedric Bosteels (UGent) , Ria Roelandt (UGent) , Annelies Emmaneel (UGent) , Sofie Van Gassen (UGent) , Louis Boon, Gert Van Isterdael (UGent) , Isabelle Guillas, Niels Vandamme (UGent) , Doris Höglinger, Bruno De Geest (UGent) , Wilfried Le Goff, Yvan Saeys (UGent) , Kodi Ravichandran (UGent) , Bart Lambrecht (UGent) and Sophie Janssens (UGent)
- Organization
- Project
-
- A novel role for the IRE1/XBP1 branch in dendritic cells: a signaling cascade matures
- Dissecting the molecular signals that drive immunogenic versus homeostatic maturation in dendritic cells. An old question revisited.
- Understanding the role of Notch in Dendritic Cell biology
- A novel role for the IRE1/XBP1 branch in dendritic cells: a signaling cascade matures.
- Synergistic engineering of anti-tumor immunity by synthethic biomaterials
- Refining cancer cell death and danger signals for the improvement of immunotherapy
- Abstract
- Dendritic cells (DCs) mature in an immunogenic or tolerogenic manner depending on the context in which an antigen is perceived, preserving the balance between immunity and tolerance. Whereas the pathways driving immunogenic maturation in response to infectious insults are well-characterized, the signals that drive tolerogenic maturation during homeostasis are still poorly understood. We found that the engulfment of apoptotic cells triggered homeostatic maturation of conventional cDC1s within the spleen. This maturation process could be mimicked by engulfment of empty, non-adjuvanted lipid nanoparticles (LNPs), was marked by intracellular accumulation of cholesterol, and highly unique to type 1 DCs. Engulfment of either apoptotic cells or cholesterol-rich LNPs led to activation of the LXR pathway, which promotes the efflux of cellular cholesterol, and repressed genes associated with immunogenic maturation. In contrast, simultaneous engagement of TLR3 to mimic viral infection via administration of poly(I:C)-adjuvanted LNPs repressed the LXR pathway, thus delaying cellular cholesterol efflux and inducing genes that promote T cell-mediated immunity. These data demonstrate that conserved cellular cholesterol efflux pathways are differentially regulated in in tolerogenic versus immunogenic cDC1s and suggest that administration of non-adjuvanted cholesterol-rich LNPs may be an approach for inducing tolerogenic DC maturation.
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01GZ10998NHTNAN3A8950VSMWF
- MLA
- Bosteels, Victor, et al. “LXR Signaling Controls Homeostatic Dendritic Cell Maturation.” SCIENCE IMMUNOLOGY, vol. 8, no. 83, 2023, doi:10.1126/sciimmunol.add3955.
- APA
- Bosteels, V., Maréchal, S., De Nolf, C., Rennen, S., Maelfait, J., Tavernier, S., … Janssens, S. (2023). LXR signaling controls homeostatic dendritic cell maturation. SCIENCE IMMUNOLOGY, 8(83). https://doi.org/10.1126/sciimmunol.add3955
- Chicago author-date
- Bosteels, Victor, Sandra Maréchal, Clint De Nolf, Sofie Rennen, Jonathan Maelfait, Simon Tavernier, Jessica Vetters, et al. 2023. “LXR Signaling Controls Homeostatic Dendritic Cell Maturation.” SCIENCE IMMUNOLOGY 8 (83). https://doi.org/10.1126/sciimmunol.add3955.
- Chicago author-date (all authors)
- Bosteels, Victor, Sandra Maréchal, Clint De Nolf, Sofie Rennen, Jonathan Maelfait, Simon Tavernier, Jessica Vetters, Evelien Van De Velde, Farzaneh Fayazpour, Kim Deswarte, Alexander Lamoot, Julie Van Duyse, Liesbet Martens, Cedric Bosteels, Ria Roelandt, Annelies Emmaneel, Sofie Van Gassen, Louis Boon, Gert Van Isterdael, Isabelle Guillas, Niels Vandamme, Doris Höglinger, Bruno De Geest, Wilfried Le Goff, Yvan Saeys, Kodi Ravichandran, Bart Lambrecht, and Sophie Janssens. 2023. “LXR Signaling Controls Homeostatic Dendritic Cell Maturation.” SCIENCE IMMUNOLOGY 8 (83). doi:10.1126/sciimmunol.add3955.
- Vancouver
- 1.Bosteels V, Maréchal S, De Nolf C, Rennen S, Maelfait J, Tavernier S, et al. LXR signaling controls homeostatic dendritic cell maturation. SCIENCE IMMUNOLOGY. 2023;8(83).
- IEEE
- [1]V. Bosteels et al., “LXR signaling controls homeostatic dendritic cell maturation,” SCIENCE IMMUNOLOGY, vol. 8, no. 83, 2023.
@article{01GZ10998NHTNAN3A8950VSMWF,
abstract = {{Dendritic cells (DCs) mature in an immunogenic or tolerogenic manner depending on the context
in which an antigen is perceived, preserving the balance between immunity and tolerance. Whereas
the pathways driving immunogenic maturation in response to infectious insults are well-characterized,
the signals that drive tolerogenic maturation during homeostasis are still poorly
understood. We found that the engulfment of apoptotic cells triggered homeostatic maturation of
conventional cDC1s within the spleen. This maturation process could be mimicked by engulfment
of empty, non-adjuvanted lipid nanoparticles (LNPs), was marked by intracellular accumulation
of cholesterol, and highly unique to type 1 DCs. Engulfment of either apoptotic cells or cholesterol-rich
LNPs led to activation of the LXR pathway, which promotes the efflux of cellular cholesterol,
and repressed genes associated with immunogenic maturation. In contrast, simultaneous
engagement of TLR3 to mimic viral infection via administration of poly(I:C)-adjuvanted LNPs
repressed the LXR pathway, thus delaying cellular cholesterol efflux and inducing genes that
promote T cell-mediated immunity. These data demonstrate that conserved cellular cholesterol
efflux pathways are differentially regulated in in tolerogenic versus immunogenic cDC1s and
suggest that administration of non-adjuvanted cholesterol-rich LNPs may be an approach for
inducing tolerogenic DC maturation.}},
articleno = {{eadd3955}},
author = {{Bosteels, Victor and Maréchal, Sandra and De Nolf, Clint and Rennen, Sofie and Maelfait, Jonathan and Tavernier, Simon and Vetters, Jessica and Van De Velde, Evelien and Fayazpour, Farzaneh and Deswarte, Kim and Lamoot, Alexander and Van Duyse, Julie and Martens, Liesbet and Bosteels, Cedric and Roelandt, Ria and Emmaneel, Annelies and Van Gassen, Sofie and Boon, Louis and Van Isterdael, Gert and Guillas, Isabelle and Vandamme, Niels and Höglinger, Doris and De Geest, Bruno and Le Goff, Wilfried and Saeys, Yvan and Ravichandran, Kodi and Lambrecht, Bart and Janssens, Sophie}},
issn = {{2470-9468}},
journal = {{SCIENCE IMMUNOLOGY}},
language = {{eng}},
number = {{83}},
pages = {{18}},
title = {{LXR signaling controls homeostatic dendritic cell maturation}},
url = {{http://doi.org/10.1126/sciimmunol.add3955}},
volume = {{8}},
year = {{2023}},
}
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