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- W2924297408 abstract "Antigen specificity is a primary goal in developing curative therapies for autoimmune disease. Dendritic cells (DCs), as the most effective antigen presenting cells in the body, represent a key target to mediate restoration of antigen-specific immune regulation. Here, we describe an injectable, dual-sized microparticle (MP) approach that employs phagocytosable ∼1 μm and nonphagocytosable ∼30 μm MPs to deliver tolerance-promoting factors both intracellularly and extracellularly, as well as the type 1 diabetes autoantigen, insulin, to DCs for reprogramming of immune responses and remediation of autoimmunity. This poly(lactic-co-glycolic acid) (PLGA) MP system prevented diabetes onset in 60% of nonobese diabetic (NOD) mice when administered subcutaneously in 8 week old mice. Prevention of disease was dependent upon antigen inclusion and required encapsulation of factors in MPs. Moreover, administration of this “suppressive-vaccine” boosted pancreatic lymph node and splenic regulatory T cells (Tregs), upregulated PD-1 on CD4+ and CD8+ T cells, and reversed hyperglycemia for up to 100 days in recent-onset NOD mice. Our results demonstrate that a MP-based platform can reeducate the immune system in an antigen-specific manner, augment immunomodulation compared to soluble administration of drugs, and provide a promising alternative to systemic immunosuppression for autoimmunity." @default.
- W2924297408 created "2019-04-01" @default.
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- W2924297408 date "2019-03-26" @default.
- W2924297408 modified "2023-10-17" @default.
- W2924297408 title "Dual-Sized Microparticle System for Generating Suppressive Dendritic Cells Prevents and Reverses Type 1 Diabetes in the Nonobese Diabetic Mouse Model" @default.
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- W2924297408 doi "https://doi.org/10.1021/acsbiomaterials.9b00332" @default.
- W2924297408 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6518351" @default.
- W2924297408 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31119191" @default.
- W2924297408 hasPublicationYear "2019" @default.
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