title: Central role for interleukin-2 in type 1 diabetes.
abstract: Type 1 diabetes presents clinically with overt hyperglycemia resulting from progressive immune-mediated destruction of pancreatic β-cells and associated metabolic dysfunction. Combined genetic and immunological studies now highlight deficiencies in both the interleukin-2 (IL-2) receptor and its downstream signaling pathway as a central defect in the pathogenesis of type 1 diabetes. Prior intervention studies in animal models indicate that augmenting IL-2 signaling can prevent and reverse disease, with protection conferred primarily by restoration of regulatory T-cell (Treg) function. In this article, we will focus on studies of type 1 diabetes noting deficient IL-2 signaling and build what we believe forms the molecular framework for their contribution to the disease. This activity results in the identification of a series of potentially novel therapeutic targets that could restore proper immune regulation in type 1 diabetes by augmenting the IL-2 pathway.
authors.affiliation: Department of Pathology, University of Florida, Gainesville, Florida, USA.
authors.forename: Maigan A
authors.initials: MA
authors.lastname: Hulme
authors.forename: Clive H
authors.initials: CH
authors.lastname: Wasserfall
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
authors.forename: Todd M
authors.initials: TM
authors.lastname: Brusko
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D008958:Models, Molecular; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2