title: 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.
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, 33101, USA.
authors.forename: Connor J
authors.initials: CJ
authors.lastname: Dwyer
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, 33101, USA.
authors.forename: Natasha C
authors.initials: NC
authors.lastname: Ward
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, 33101, USA.|Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, 33101, USA.|Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Miller School of Medicine, University of Miami, Miami, FL, 33101, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pugliese
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, 33101, USA. tmalek@med.miami.edu.|Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, 33101, USA. tmalek@med.miami.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Malek
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000276:immunology*; D012307:Risk Factors; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D007376:Interleukin-2
keywords: IL-2; IL-2 receptor; Low-dose IL-2 therapy; Tolerance; Tregs; Type 1 diabetes