Promoting Immune Regulation in Type 1 Diabetes Using Low-Dose Interleukin-2

Abstract

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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Acknowledgments

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.

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Correspondence to Thomas R. Malek.

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Connor J. Dwyer, Natasha C. Ward, Alberto Pugliese, and Thomas R. Malek declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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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

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Keywords

  • Type 1 diabetes
  • IL-2
  • Tregs
  • Low-dose IL-2 therapy
  • IL-2 receptor
  • Tolerance