ArticleGene therapy2014
Expression of IL-2 in β cells by AAV8 gene transfer in pre-diabetic NOD mice prevents diabetes through activation of FoxP3-positive regulatory T cells.
Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Rheb1 signaling and the fate of pancreatic β cells: Toward a new frontier in diabetes therapy.World journal of diabetes · 2025Article
- Cytokine Couture: Designer IL2 Molecules for the Treatment of Disease.ImmunoTargets and therapy · 2025Review
- Review
- T cells and their products in diabetic kidney disease.Frontiers in immunology · 2023Review
- Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection.International journal of molecular sciences · 2021Review
- The Role of T Cell Receptor Signaling in the Development of Type 1 Diabetes.Frontiers in immunology · 2020Review
- Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors.JCI insight · 2019Article
- Gene Therapy with an Adeno-Associated Viral Vector Expressing Human Interleukin-2 Alters Immune System Homeostasis in Humanized Mice.Human gene therapy · 2018Article
- Therapies to Suppress β Cell Autoimmunity in Type 1 Diabetes.Frontiers in immunology · 2018Review
- Exocytosis proteins as novel targets for diabetes prevention and/or remediation?American journal of physiology. Regulatory, integrative and comparative physiology · 2017Review
- The contribution of interleukin-2 to effective wound healing.Experimental biology and medicine (Maywood, N.J.) · 2017Review
- Efficient Gene Delivery and Expression in Pancreas and Pancreatic Tumors by Capsid-Optimized AAV8 Vectors.Human gene therapy methods · 2017Article
- Transgene and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus.Nano reviews & experiments · 2017Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We previously demonstrated that intraperitoneal delivery of adeno-associated virus serotype 8 (AAV8) stably transduces the pancreas, including the β cells in the pancreatic islets. We further demonstrated the ability to deliver and express target genes specifically in β cells for at least 6 months using a murine insulin promoter in a double-stranded, self-complementary AAV vector. Recombinant interleukin (IL)-2 has been shown to induce CD4(+)CD25(+) regulatory T cells (Tregs) in several mouse models of autoimmune disease. Here we evaluated the effects of double-stranded adeno-associated virus serotype 8-mouse insulin promoter (dsAAV8-mIP)-mediated delivery of 2 to pancreatic β cells in non-obese diabetic (NOD) mice. AAV8-mIP-mediated gene expression of IL-2 to pancreatic β cells of 10-week-old NOD mice prevented the onset of hyperglycemia in NOD mice more in a dose-dependent manner with the lower dose of virus being more effective than a higher dose of AAV-mIP-IL-2 and IL-4. Moreover, the local β-cell expression of IL-2 increased the number of CD4(+)CD25(+)FoxP3(+) cells in the pancreatic lymph node (PLN) and SPL in both NOD and C57BL/6 mice. Taken together, these results demonstrate that local, low expression of mIL-2 in islets prevents progress of diabetes through the regulation of Tregs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.