Lipid nanoparticles as a tool to dissect dendritic cell maturation pathways
Depending on how antigens are being decoded by dendritic cells (DCs), their acquisition will induce a homeostatic or immunogenic maturation program. This determines how antigens are being presented and whether DCs instruct T cells to induce tolerance or immunity. So far, the field lacks proper tools to distinguish the two maturation states. By using a lipid nanoparticle (LNP)-based approach and cellular indexing of transcriptomes and epitopes sequencing analysis, we designed a flow cytometry panel and transcriptional profiling tools to reliably annotate the two DC maturation states. The data corroborate that uptake of empty (or peptide-containing) LNPs induces homeostatic maturation in DCs, while uptake of Toll-like receptor ligand-adjuvanted (or mRNA-containing) LNPs induces immunogenic maturation, yielding distinct T cell outputs. This reveals that LNPs are not decoded as "dangerous" by DCs, and that the cargo is essential to provide adjuvant activity, which is highly relevant for the targeted design of LNP-based therapies.
Authors
- Ine Lentacker (ORCID: https://orcid.org/0000-0001-7492-6568)
- Kevin Verstaen (ORCID: https://orcid.org/0000-0003-3582-0298)
- Niels Vandamme (ORCID: https://orcid.org/0000-0001-6582-0040)
- Sofie Rennen (ORCID: https://orcid.org/0000-0002-2411-2045)
- Rein Verbeke (ORCID: https://orcid.org/0000-0003-1849-5411)
- Ria Roelandt (ORCID: https://orcid.org/0000-0001-9936-7555)
- Victor Bosteels (ORCID: https://orcid.org/0000-0001-8838-021X)
- Stijn Vanhee (ORCID: https://orcid.org/0000-0001-5305-1651)
- Sandra Maréchal (ORCID: https://orcid.org/0000-0002-1275-3486)
- Farzaneh Fayazpour (ORCID: https://orcid.org/0000-0001-5469-1853)
- Bruno G. De Geest (ORCID: https://orcid.org/0000-0001-9826-6170)
- Karine Breckpot (ORCID: https://orcid.org/0000-0003-4331-3480)
- Stefaan C. De Smedt (ORCID: https://orcid.org/0000-0002-8653-2598)
- Clint De Nolf (ORCID: https://orcid.org/0000-0002-2033-1830)
- Janne Swinnen
- Sophie Janssens (ORCID: https://orcid.org/0000-0003-1702-1636)
- Evelien Van De Velde (ORCID: https://orcid.org/0000-0003-4125-2952)
- Greta R. Webb (ORCID: https://orcid.org/0000-0003-0348-3119)
- Eric A. J. Hoste (ORCID: https://orcid.org/0000-0001-9301-8055)
- Jessica Vetters (ORCID: https://orcid.org/0000-0001-5817-0086)
- Philippe Gevaert (ORCID: https://orcid.org/0000-0002-1629-8468)
- Karo Van Lil
Institutions
- Vrije Universiteit Brussel (BE)
- Ghent University Hospital (BE)
- Ghent University (BE)
- VIB-UGent Center for Plant Systems Biology (BE)
- VIB-UGent Center for Inflammation Research (BE)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-08-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.116150
- Citations
- 12
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 9.57
Funders
- Universiteit Leiden
- Fonds Wetenschappelijk Onderzoek
- Universiteit Gent
- Leids Universitair Medisch Centrum
- European Research Council