The crucial role of IL-2/IL-2RA-mediated immune regulation in the pathogenesis of type 1 diabetes, an evidence coming from genetic and animal model studies.
Interleukin-2 (IL-2) plays an established role in T-cell regulation through binding to the high-affinity IL-2 receptor (IL-2R). The alpha-chain encoded by the IL2RA (CD25) gene is a substantial component of the high-affinity receptor molecule highly expressed by activated T lymphocytes. Recently, a strong evidence was obtained for the involvement of IL-2RA in conferring susceptibility to type 1 diabetes (T1D). Significant association with T1D was also found in the region on chromosome 4q27 containing the IL2 gene and homologous to the susceptibility locus idd3 in non-obese diabetic (NOD) mice, an animal model for human T1D. Here we focus on the discussion of these new findings suggesting for a crucial role of IL-2/IL-2RA-mediated regulatory mechanisms in preventing T1D. The non-redundant role of IL-2 and its receptor in etiology of T1D could be particularly attributable to the regulation of CD4+ CD25+ regulatory T cells, whose function is critical in maintaining immune homeostasis.
Chistiakov
Dimitry A
DA
Department of Pathology, University of Pittsburgh Medical Center, A719 Scaife Hall, Pittsburgh, PA 15261, USA. dimitry.chistiakov@eudoramail.com
Voronova
Natalia V
NV
Chistiakov
Pavel A
PA
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
D007376:Interleukin-2; D015375:Receptors, Interleukin-2