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Lipid nanoparticles as a tool to dissect dendritic cell maturation pathways.

Sofie Rennen1, Victor Bosteels1, Clint De Nolf2

  • 1Laboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.

Cell Reports
|August 19, 2025
PubMed
Summary

Lipid nanoparticles (LNPs) can induce either homeostatic or immunogenic maturation in dendritic cells (DCs), depending on their cargo. This discovery is key for designing effective LNP-based therapies and vaccines.

Keywords:
CITE-sequencingCP: ImmunologyToll-like receptoradjuvanticitydendritic cellshomeostatic maturationimmunityimmunogenic maturationlipid nanoparticlematurationtolerance

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Area of Science:

  • Immunology
  • Cell Biology
  • Nanotechnology

Background:

  • Dendritic cells (DCs) play a crucial role in immune responses by presenting antigens and instructing T cells.
  • The maturation state of DCs, either homeostatic or immunogenic, dictates whether tolerance or immunity is induced.
  • Current methods lack reliable tools to distinguish between these two DC maturation states.

Purpose of the Study:

  • To develop tools for reliably distinguishing between homeostatic and immunogenic dendritic cell maturation states.
  • To investigate how lipid nanoparticles (LNPs) influence DC maturation and subsequent T cell responses.

Main Methods:

  • Utilized a lipid nanoparticle (LNP)-based approach combined with cellular indexing of transcriptomes and epitopes sequencing.
  • Designed a flow cytometry panel and transcriptional profiling tools for annotating DC maturation states.
  • Analyzed DC responses to different LNP formulations (empty, peptide-containing, adjuvant-adjuvanted, mRNA-containing).

Main Results:

  • Uptake of empty or peptide-containing LNPs induced homeostatic DC maturation.
  • Uptake of Toll-like receptor ligand-adjuvanted or mRNA-containing LNPs induced immunogenic DC maturation.
  • Distinct T cell outputs were observed depending on the LNP-induced DC maturation state.

Conclusions:

  • Lipid nanoparticles (LNPs) are not inherently perceived as 'dangerous' by dendritic cells.
  • The cargo within LNPs is essential for providing adjuvant activity and directing immune responses.
  • Findings are highly relevant for the targeted design of LNP-based therapies and vaccines.