IL-2 and its high-affinity receptor: Genetic control of immunoregulation and autoimmunity

Type 1 diabetes (T1D) is an organ-specific autoimmune disease featured by destruction of the insulin producing beta-cells of the pancreas by autoreactive T-lymphocytes. Putative environmental triggers conspire with a constellation of genetic elements scattered throughout the genome to elicit a multifactorial autoimmune response involving virtually every cell type of the immune system against pancreatic beta-cells. Recent highly powered genome-wide association studies have confirmed and identified fifteen chromosomal regions harboring several candidate T1D-associated gene loci. Here, we summarize what we know about the genetics of T1D with an emphasis on the contributions of mouse IL2 and human IL2RA polymorphisms and the IL-2-IL-2R pathway to autoimmunity and, more specifically, Treg development and function. (C) 2009 Elsevier Ltd. All rights reserved.