Belgian researchers detailed how lipid nanoparticles (LNPs), foundational to mRNA vaccine platforms, dictate the maturation pathways of dendritic cells (DCs), key orchestrators of immune responses. LNPs carrying mRNA or Toll-like receptor ligands induce immunogenic DC maturation and T cell activation, whereas empty or peptide-loaded LNPs promote a homeostatic, anti-inflammatory program. This cargo-dependent mechanism enables targeted immune modulation, crucial for vaccine design and autoimmune disease therapies.<BR><BR>The findings suggest that the immune system decodes LNPs primarily based on their payload rather than their lipid shell, providing avenues to tailor safer and more effective nanoparticle-based therapeutics.