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.
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