Induction of Antigen-Specific Immune Suppression Using Biodegradable Nanoparticles Containing Antigen and Dexamethasone

Abstract

Abstract Dexamethasone (Dex) is known to reduce inflammation and autoimmunity by modulating dendritic cell (DC) function, maturation, and differentiation. Nanoparticles (NPs) prepared using biodegradable and biocompatible poly(lactic-co-glycolic acid) (PLGA) can be used to target-delivery vehicles to DCs. In the present study, PLGA nanoparticles containing ovalbumin (OVA) and Dex (NP[OVA+Dex]) were prepared by W1/O/W2 double emulsion solvent evaporation method, and evaluated their antigen-specific immune tolerizing effects. DCs treated with NP[OVA+Dex] were decreased in the expression of MHC class II (I-Ab) and co-stimulatory molecules (CD80 and CD86), and increased in the proportion of CD86−PD-L1+ cell population. DCs treated with NP[OVA+Dex] were reduced in the production of pro-inflammatory cytokine, such as IL-1β, IL-6, IL-12p40 and TNF-α, whereas the production of immunosurpressive cytokine IL-10 was enhanced. Treatment of DCs with NP[OVA+Dex] were diminished in MHC class II-restricted OVA presentation and allogenic T cell stimulatory capacity. NP[OVA+Dex]-treated DCs induced CD4+CD25+FoxP3+ regulatory T cell differentiation from CD4+CD25− T cells isolated from normal, or OT-II mice. Mice injected i.v., or i.g. with NP[OVA+Dex] were suppressed in both inducing OVA-specific CTL responses and producing OVA-specific IgG. The present study demonstrates that NPs encapsulated with antigen and Dex are useful tools in inducing antigen-specific immune tolerance.