Immune Netw.  2019 Jun;19(3):e19. 10.4110/in.2019.19.e19.

Polymeric Nanoparticles Containing Both Antigen and Vitamin D₃ Induce Antigen-Specific Immune Suppression

• Jung HH
• Kim SH
• Moon JH
• Jeong SU
• Jang S
• Park CS
• Lee CK

• KMID: 2450204
• DOI: http://doi.org/10.4110/in.2019.19.e19

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.

Keyword

Polymeric nanoparticle; Vitamin D₃; Dendritic cells; Treg cells; Antigen-specific immune suppression

MeSH Terms

Animals
Antigen-Presenting Cells
Autoimmune Diseases
Cholecalciferol
Cytokines
Dendritic Cells
Hypercalcemia
Immune Tolerance
Injections, Intravenous
Interleukin-10
Methods
Mice
Nanoparticles*
Ovalbumin
Polymers*
T-Lymphocytes, Regulatory
Vitamins*
Cholecalciferol
Cytokines
Interleukin-10
Ovalbumin
Polymers
Vitamins