Dual-Sized Microparticle System for Generating Suppressive Dendritic Cells Prevents and Reverses Type 1 Diabetes in the Nonobese Diabetic Mouse Model
| Autor: | Benjamin G. Keselowsky, Natalia V. Dolgova, Todd M. Brusko, Chang-Qing Xia, Mark A. Atkinson, Michael J. Clare-Salzler, Matthew R. Carstens, Gregory P Marshall, Clive Wasserfall, Ying Zhang, Joshua M. Stewart, Jamal S. Lewis |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
type 1 diabetes
dendritic cell 0206 medical engineering Biomedical Engineering 02 engineering and technology Nod medicine.disease_cause Autoimmune Disease Autoimmunity Vaccine Related Biomaterials Immune system Antigen trafficking Medicine Antigen-presenting cell Metabolic and endocrine Autoimmune disease Type 1 diabetes treatment business.industry Prevention Inflammatory and immune system Diabetes biomaterial PLGA Dendritic cell 021001 nanoscience & nanotechnology medicine.disease 020601 biomedical engineering microparticle Cancer research Immunization 0210 nano-technology business |
| Zdroj: | ACS biomaterials science & engineering, vol 5, iss 5 |
| ISSN: | 2373-9878 |
| DOI: | 10.1021/acsbiomaterials.9b00332 |
| Popis: | [Image: see text] 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|