Dysregulation of the immune system contributes to the breakdown of immune regulation, leading to autoimmune diseases, such as type 1 diabetes (T1D). Current therapies for T1D include daily insulin, due to pancreatic β-cell destruction to maintain blood glucose levels, suppressive immunotherapy to decrease the symptoms associated with autoimmunity, and islet transplantation. Genetic risks for T1D have been linked to IL-2 and IL-2R signaling pathways that lead to the breakdown of self-tolerance mechanisms, primarily through altered regulatory T cell (Treg) function and homeostasis. In attempt to correct such deficits, therapeutic administration of IL-2 at low doses has gained attention due to the capacity to boost Tregs without the unwanted stimulation of effector T cells. Preclinical and clinical studies utilizing low-dose IL-2 have shown promising results to expand Tregs due to their high selective sensitivity to respond to IL-2. These results suggest that low-dose IL-2 therapy represents a new class of immunotherapy for T1D by promoting immune regulation rather than broadly suppressing unwanted and beneficial immune responses.
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Our work was supported by the National Institutes of Health (R01 DK093866, R01 AI055815), the American Diabetes Association (1-15-BS-125), Wallace H. Coulter Center for Translational Research, and Diabetes Research Institute Foundation, Hollywood, FL, the Peacock Foundation, Inc., Miami, FL.
Conflict of Interest
Connor J. Dwyer, Natasha C. Ward, Alberto Pugliese, and Thomas R. Malek declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Immunology and Transplantation
Connor J. Dwyer and Natasha C. Ward contributed equally to this work.
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Dwyer, C.J., Ward, N.C., Pugliese, A. et al. Promoting Immune Regulation in Type 1 Diabetes Using Low-Dose Interleukin-2. Curr Diab Rep 16, 46 (2016). https://doi.org/10.1007/s11892-016-0739-1
- Type 1 diabetes
- Low-dose IL-2 therapy
- IL-2 receptor