Tolerogenic Dendritic Cell- and M2 Macrophage Polarization-Inducible Hybrid Nanoparticles Alleviate Asthma in Mice.

Abstract

Asthma is a chronic allergic inflammatory disease of the airways that can have fatal effects by impairing the oxygen transport function of the lungs. In this study, asthma is treated using a drug delivery system that has recently garnered increased attention. To suppress the activity of immune cells involved in asthma, dexamethasone (Dex) is loaded on a poly lactic-<i>co</i>-glycolic acid polymer and wrapped in lipid-containing monophosphoryl lipid A (MPLA), a toll-like receptor 4 (TLR4) ligand. Our results revealed that the hybrid nanoparticles containing Dex and MPLA (DM-HNPs) effectively target dendritic cells (DCs) and macrophages and inhibit the activation of these cells in mice. Moreover, DM-HNP increases the production of interleukin-10 (IL-10) in the alum-stimulated DCs and macrophages, indicating its promotion of tolerogenic DC and M2 macrophage differentiation, respectively. DM-HNPs further induce the generation of regulatory T cells. Therefore, DM-HNP is effective in suppressing the onset of asthma and treating it through regulatory T cell generation. Overall, DM-HNPs alleviate asthma-induced by immune regulatory cells and can serve as a potential treatment for patients with asthma.