ArticleProceedings of the National Academy of Sciences of the United States of America2009
Loss of parity between IL-2 and IL-21 in the NOD Idd3 locus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 63 citations in OpenAlex.
- Aberrant IL-21/STAT3 signaling disrupts regulatory T cell function and CD4Frontiers in immunology · 2026Article
- Advancing Animal Models of Human Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Blimp-1 molds the epigenetic architecture of IL-21-mediated autoimmune diseases through an autoregulatory circuit.JCI insight · 2022Article
- Association of interleukin-2, interleukin-21 and interleukin-23 with hyperlipidemia in pediatric type 1 diabetes.Molecular biology reports · 2021Article
- The Common Cytokine Receptor γ Chain Family of Cytokines.Cold Spring Harbor perspectives in biology · 2018Review
- Thymic B Cell-Mediated Attack of Thymic Stroma Precedes Type 1 Diabetes Development.Frontiers in immunology · 2018Article
- The Role of NOD Mice in Type 1 Diabetes Research: Lessons from the Past and Recommendations for the Future.Frontiers in endocrinology · 2018Article
- Altered homeostasis and development of regulatory T cell subsets represent an IL-2R-dependent risk for diabetes in NOD mice.Science signaling · 2017Article
- IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2.Nature communications · 2017Article
- The circadian gene Arntl2 on distal mouse chromosome 6 controls thymocyte apoptosis.Mammalian genome : official journal of the International Mammalian Genome Society · 2017Article
- CD4 T cell differentiation in type 1 diabetes.Clinical and experimental immunology · 2016Review
- Interleukin-21 plays a critical role in the pathogenesis and severity of type I autoimmune hepatitis.SpringerPlus · 2016Article
- Sleeping Beauty Transposon Mutagenesis as a Tool for Gene Discovery in the NOD Mouse Model of Type 1 Diabetes.G3 (Bethesda, Md.) · 2015Article
- Article
- A T cell extrinsic mechanism by which IL-2 dampens Th17 differentiation.Journal of autoimmunity · 2015Article
- Expression of IL-2 in β cells by AAV8 gene transfer in pre-diabetic NOD mice prevents diabetes through activation of FoxP3-positive regulatory T cells.Gene therapy · 2014Article
- Congenic mice reveal genetic epistasis and overlapping disease loci for autoimmune diabetes and listeriosis.Immunogenetics · 2014Article
- Article
- β-cell-specific IL-2 therapy increases islet Foxp3+Treg and suppresses type 1 diabetes in NOD mice.Diabetes · 2013Article
- Distinct genetic control of autoimmune neuropathy and diabetes in the non-obese diabetic background.Journal of autoimmunity · 2013Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-2 and IL-21 are two cytokines with great potential to affect autoimmune infiltration of nonlymphoid tissue, and are contained within the strongest non-MHC-linked locus for type 1 diabetes (T1D) susceptibility on the nonobese diabetic (NOD) mouse (Idd3). IL-21 is necessary for the development of diabetes in the NOD mouse, but a number of important studies argue that decreased expression of IL-2 explains Idd3. In this study, we demonstrate that the amount of IL-21, but not IL-2, correlated with T1D incidence. During our analyses of the IL-2/IL-21 interval, we found that mice segregate into one of two distinct expression profiles. In the first group, which includes the C57BL/6 strain, both Il2 and Il21 were expressed at low levels. In the other group, which includes the NOD strain, Il2 and Il21 were both highly expressed. However, because NOD IL-2 mRNA was relatively unstable, IL-2 production was remarkably similar between strains. The increased production of IL-21 in NOD mice was found to result from two single nucleotide polymorphisms within the distal promoter region that conferred increased binding affinity for the transcription factor Sp1. Our findings indicate that a loss of locus parity after decreased IL-2 mRNA stability ensures that the high-expressing IL-21 allele persists in nature and provides a basis for autoimmunity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.