期刊
CURRENT DIABETES REPORTS
卷 16, 期 6, 页码 -出版社
CURRENT MEDICINE GROUP
DOI: 10.1007/s11892-016-0739-1
关键词
Type 1 diabetes; IL-2; Tregs; Low-dose IL-2 therapy; IL-2 receptor; Tolerance
资金
- National Institutes of Health [R01 DK093866, R01 AI055815]
- American Diabetes Association [1-15-BS-125]
- Wallace H. Coulter Center for Translational Research
- Diabetes Research Institute Foundation, Hollywood, FL
- Peacock Foundation, Inc., Miami, FL.
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 beta-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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