Polymeric Nanoparticles Containing Both Antigen and Vitamin D3 Induce Antigen-Specific Immune Suppression
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초록
The active form of vitamin D3, 1,25-dihydroxyvitamin D3 (aVD3), is known to exert beneficial effects in the treatment of autoimmune diseases because of its immunosuppressive effects. However, clinical application of aVD3 remains limited because of the potential side effects, particularly hypercalcemia. Encapsulation of aVD3 within biodegradable nanoparticles (NPs) would enhance the delivery of aVD3 to antigen presenting cells, while preventing the potential systemic side effects of aVD3. In the present study, polymeric NPs containing ovalbumin (OVA) and aVD3 (NP[OVA+aVD3]) were prepared via the water-in-oil-in-water double emulsion solvent evaporation method, after which their immunomodulatory effects were examined. Bone marrow-derived immature dendritic cells (DCs) treated with NP(OVA+aVD3) did not mature into immunogenic DCs but were converted into tolerogenic DCs, which express low levels of co-stimulatory molecules and MHC class II molecules, produce lower levels of pro-inflammatory cytokines while increasing the production of IL-10 and TGF-β, and induce the generation of Tregs. Intravenous injection with NP(OVA+aVD3) markedly suppressed the generation of OVA-specific CTLs in mice. Furthermore, OVA-specific immune tolerance was induced in mice orally administered with NP(OVA+aVD3). These results show that biodegradable NPs encapsulating both antigen and aVD3 can effectively induce antigen-specific immune suppression.
Abstract
The active form of vitamin D3, 1,25-dihydroxyvitamin D3 (aVD3), is known to exert beneficial effects in the treatment of autoimmune diseases because of its immunosuppressive effects. However, clinical application of aVD3 remains limited because of the potential side effects, particularly hypercalcemia. Encapsulation of aVD3 within biodegradable nanoparticles (NPs) would enhance the delivery of aVD3 to antigen presenting cells, while preventing the potential systemic side effects of aVD3. In the present study, polymeric NPs containing ovalbumin (OVA) and aVD3 (NP[OVA+aVD3]) were prepared via the water-in-oil-in-water double emulsion solvent evaporation method, after which their immunomodulatory effects were examined. Bone marrow-derived immature dendritic cells (DCs) treated with NP(OVA+aVD3) did not mature into immunogenic DCs but were converted into tolerogenic DCs, which express low levels of co-stimulatory molecules and MHC class II molecules, produce lower levels of pro-inflammatory cytokines while increasing the production of IL-10 and TGF-β, and induce the generation of Tregs. Intravenous injection with NP(OVA+aVD3) markedly suppressed the generation of OVA-specific CTLs in mice. Furthermore, OVA-specific immune tolerance was induced in mice orally administered with NP(OVA+aVD3). These results show that biodegradable NPs encapsulating both antigen and aVD3 can effectively induce antigen-specific immune suppression.
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