期刊
CLINICAL IMMUNOLOGY
卷 160, 期 1, 页码 90-102出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2015.03.023
关键词
Microparticle; Dendritic cells; Tolerance; NOD; Diabetes; Prevention
类别
资金
- NIH NIDDK [R01DK098589, R01 DK091658]
- NIAID [AI42288, R21A1094360]
- Blanche J. Salisbury Diabetes Research Fund
We developed a novel poly(lactic-co-glycolic acid)-based, microparticle (MP) system providing concurrent delivery of multiple encapsulated immuno-suppressive factors and antigen, for in vivo conditioning of dendritic cells (DCs) toward a tolerance promoting pathway. Subcutaneous administration prevents onset of type 1 diabetes (T1D) in NOD mice. Two MP sizes were made: phagocytosable MPs were fabricated encapsulating vitamin D3 or insulin B(9-23) peptide, while unphagocytosable MPs were fabricated encapsulating TGF-beta 1 or GM-CSF. The combination of Vit D3/TGF-beta 1 MPs confers an immature and LPS activation-resistant phenotype to DCs, and MP-delivered antigen is efficiently and functionally presented. Notably, two subcutaneous injections into 4 week old NOD mice using the combination of MPs encapsulating Vit D3, Ins B, TGF-beta 1 and GM-CSF protected 40% of mice from T1D development, significant in comparison to the control. This work represents one of the first applications of a biomaterial-based, MP vaccine system to successfully prevent autoimmune diabetes. (C) 2015 Elsevier Inc. All rights reserved.
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