| http://purl.uniprot.org/citations/29259102 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29259102 | http://www.w3.org/2000/01/rdf-schema#comment | "The cytokine interleukin-2 (IL-2) is critical for the functions of regulatory T cells (Tregs). The contribution of polymorphisms in the gene encoding the IL-2 receptor α subunit (IL2RA), which are associated with type 1 diabetes, is difficult to determine because autoimmunity depends on variations in multiple genes, where the contribution of any one gene product is small. We investigated the mechanisms whereby a modest reduction in IL-2R signaling selectively in T lymphocytes influenced the development of diabetes in the NOD mouse model. The sensitivity of IL-2R signaling was reduced by about two-to threefold in Tregs from mice that coexpressed wild-type IL-2Rβ and a mutant subunit (IL-2RβY3) with reduced signaling (designated NOD-Y3). Male and female NOD-Y3 mice exhibited accelerated diabetes onset due to intrinsic effects on multiple activities in Tregs Bone marrow chimera and adoptive transfer experiments demonstrated that IL-2RβY3 Tregs resulted in impaired homeostasis of lymphoid-residing central Tregs and inefficient development of highly activated effector Tregs and that they were less suppressive. Pancreatic IL-2RβY3 Tregs showed impaired development into IL-10-secreting effector Tregs The pancreatic lymph nodes and pancreases of NOD-Y3 mice had increased numbers of antigen-experienced CD4+ effector T cells, which was largely due to impaired Tregs, because adoptively transferred pancreatic autoantigen-specific CD4+ Foxp3- T cells from NOD-Y3 mice did not accelerate diabetes in NOD.SCID recipients. Our study indicates that the primary defect associated with chronic, mildly reduced IL-2R signaling is due to impaired Tregs that cannot effectively produce and maintain highly functional tissue-seeking effector Treg subsets."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.org/dc/terms/identifier | "doi:10.1126/scisignal.aam9563"xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/author | "Chen Z."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/author | "Yu L."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/author | "Fotino C."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/author | "Malek T.R."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/author | "Toomer K.H."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/author | "Dwyer C.J."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/author | "Bayer A.L."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/author | "Ward N.C."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/author | "Cabello-Kindelan C."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/name | "Sci Signal"xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/pages | "eaam9563"xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/title | "Altered homeostasis and development of regulatory T cell subsets represent an IL-2R-dependent risk for diabetes in NOD mice."xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/29259102 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29259102 |
| http://purl.uniprot.org/citations/29259102 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29259102 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YWF2-mappedCitation-29259102 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29259102 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YXM4-mappedCitation-29259102 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29259102 |
| http://purl.uniprot.org/uniprot/#_A1E2H6-mappedCitation-29259102 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29259102 |
| http://purl.uniprot.org/uniprot/#_P16297-mappedCitation-29259102 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29259102 |
| http://purl.uniprot.org/uniprot/#_Q05C79-mappedCitation-29259102 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29259102 |
| http://purl.uniprot.org/uniprot/#_P06800-mappedCitation-29259102 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29259102 |