title: The IL-2/CD25 pathway determines susceptibility to T1D in humans and NOD mice.
abstract: Although the interleukin-2 (IL-2)/IL-2R signaling pathway has been the focus of numerous studies, certain aspects of its molecular regulation are not well characterized, especially in non-T cells, and a more complete understanding of the pathway is necessary to discern the functional basis of the genetic association between the IL-2-IL-21 and IL-2RA/CD25 gene regions and T1D in humans. Genetic variation in these regions may promote T1D susceptibility by influencing transcription and/or splicing and, hence, IL-2 and IL-2RA/CD25 expression at the protein level in different immune cell subsets; thus, there is a need to establish links between the genetic variation and immune cell phenotypes and functions in humans, which can be further investigated and validated in mouse models. The detection and characterization of genetically determined immunophenotypes should aid in elucidating disease mechanisms and may enable future monitoring of disease initiation and progression in prediabetic subjects and of responses to therapeutic intervention.
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 OXY, UK.
authors.forename: Calliope A
authors.initials: CA
authors.lastname: Dendrou
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wicker
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D015551:Autoimmunity; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D055611:Natural Killer T-Cells / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit
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