Lipid nanoparticles as a tool to dissect dendritic cell maturation pathways

2025/08/01 by Sofie Rennen, Victor Bosteels, Clint De Nolf +19 · 1 voice
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · #Immunotherapy and Immune Responses #RNA Interference and Gene Delivery #Immune Cell Function and Interaction

paper · pdf · doi:10.1016/j.celrep.2025.116150

openalex publication_date 2025/08/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

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.

Citations

• The JAK-STAT Pathway: Impact on Human Disease and Therapeutic Intervention
• limma powers differential expression analyses for RNA-sequencing and microarray studies
• A conserved dendritic-cell regulatory program limits antitumour immunity
• Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
• Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
• Dendritic Cells Revisited
• Integrated analysis of multimodal single-cell data
• Decoding immunogenic cell death from a dendritic cell perspective
• NF-κB in biology and targeted therapy: new insights and translational implications
• Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer

Discussions

• Out this week: another example of @viblifesciences.bsky.social’s cores powering discovery. LNPs cue dendritic cells via their cargo—not the lipids. The team also built a readout for “immunogenic” vs [bsky, 0 points, 0 comments]