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Immunotherapy With Low-Dose IL-2/CD25 Prevents β-Cell Dysfunction and Dysglycemia in Prediabetic NOD Mice.
- Source :
- Diabetes; Jun2023, Vol. 72 Issue 6, p769-780, 12p
- Publication Year :
- 2023
-
Abstract
- Low-dose IL-2 is a promising immunotherapy in clinical trials for treating type 1 diabetes. A new IL-2 analog, IL-2/CD25 fusion protein, has been shown to more efficiently delay or prevent diabetes in NOD mice by expanding the population of activated regulatory T cells. This therapy is intended for use before clinical diagnosis, in the early stages of type 1 diabetes progression. During this prediabetic period, there is a chronic decline in β-cell function that has long-term implications for disease pathogenesis. Yet, to date, the effects of IL-2/CD25 on β-cell function have not been evaluated. In this study, we treated prediabetic NOD mice with low-dose mouse IL-2/CD25 over 5 weeks and determined its impact on β-cell function. This treatment limited the progressive impairment of glucose tolerance and insulin secretion typical of the later stages of prediabetes. Intracellular Ca<superscript>2+</superscript> responses to glucose in β-cells became more robust and synchronous, indicating that changing the local immune cell infiltrate with IL-2/CD25 preserved β-cell function even after treatment cessation. Our study thus provides mechanistic insight and serves as a steppingstone for future research using low-dose IL-2/CD25 immunotherapy in patients. Article Highlights: Immunotherapies such as IL-2/CD25 are known to prevent or delay diabetes. However, their impact on individual β-cell function is not yet understood. Female NOD mice progress from stage 1 to 2 pre–type 1 diabetes between 12 and 17 weeks. Treatment with mouse IL-2 (mIL-2)/CD25 prevents this progression even after treatment cessation. Individual β-cell function (measured via intracellular Ca<superscript>2+</superscript> responses to glucose) declines during the pathogenesis of type 1 diabetes. Treatment with mIL-2/CD25 therapy limits β-cell dysfunction, and function continues to improve after treatment cessation. Insulin secretion is improved with mIL-2/CD25 therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 72
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 163842817
- Full Text :
- https://doi.org/10.2337/db22-0482