Combined Administration of Plasmids Encoding IL-4 and IL-10 Prevents the Development of Autoimmune Diabetes in Nonobese Diabetic Mice
Open accessAbstract
Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet beta-cell destruction belong to the Th1 subset (producing IL-2 and IFN-gamma), whereas regulatory T cells are Th2 type (producing IL-4 and IL-10). Here, we evaluate the effect of combined delivery of plasmid DNA encoding IL-4 and IL-10 using a degradable, cationic polymeric carrier, poly[gamma-(4-aminobutyl)-L-glycolic acid] (PAGA), in nonobese diabetic (NOD) mice. In the liver of NOD mice, we detected mouse Il4 and Il10 mRNA 5 days after intravenous injection of both PAGA-Il4 and PAGA-Il10 plasmid complexes. We found that 6 weeks after injection, 75% of observed islets were intact compared with less than 3% in the control group. Furthermore, in the treatment group, only 5% of the islets were severely infiltrated by the lymphocytes compared with over 30% in the control group. We measured glucose levels weekly up to the age of 32 weeks, revealing that co-injection of PAGA-Il4 and PAGA-Il10 plasmids prevented the development of diabetes in 75% of the treated animals. Thus, combined administration of mouse Il4 and Il10 plasmids prevents the development of autoimmune diabetes in NOD mice.
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DNA encoding IL-10 and IL-4 encapsulated in polymeric nanoparticles delivered into white blood cells inhibits T cell response against residual native islet cells in prediabetic animal model, inhibiting diabetes development in 75% of animals.
“DNA encoding interleukin (IL)-10 and IL-4 encapsulated in polymeric nanoparticles has been delivered into white blood cells to inhibit the T cell response against residual native islet cells in a prediabetic animal model. It was found to be very helpful in diabetic management because it inhibited diabetes development in 75% of the animals.94”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [94]
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Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles
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- Authors
- Ko, K. S., Lee, M., Koh, J. J., & Kim, S. W.
- Affiliations
- University of Utah (US)
- Corresponding author
- Kim, Sung Wan
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 4
- Issue
- 4
- Pages
- 313-316
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W2011655318
- Cited by
- 97
- References
- 28
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 1 · 2017: 4 · 2015: 1 · 2014: 5 · 2013: 3
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- autoimmune diabetes, NOD mice, IL-4, IL-10, Paga, beta cell destruction, diabetes prevention
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Female, Genetic Vectors, Glucose, Injections, Intravenous, Islets of Langerhans, Liver, Plasmids, RNA, Messenger, Genetic Therapy, Interleukin-4, Mice, Inbred NOD, Interleukin-10, Reverse Transcriptase Polymerase Chain Reaction, Mice
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