ArticlePloS one2009
Apoptosis of CD4+ CD25(high) T cells in type 1 diabetes may be partially mediated by IL-2 deprivation.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 86 citations in OpenAlex.
- Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function.Journal of immunology (Baltimore, Md. : 1950) · 2012Trial
- Imbalance of stem-like and effector T cell states in children with early type 1 diabetes across conventional and regulatory subsets.Nature communications · 2025Article
- Blood methylome signatures in children exposed to maternal type 1 diabetes are linked to protection against islet autoimmunity.Nature metabolism · 2025Article
- Genetic Polymorphism ofMedicina (Kaunas, Lithuania) · 2022Review
- Article
- Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes.Nature metabolism · 2022Article
- Expression of Ferroptosis-Related Genes is Correlated with Immune Microenvironment in Diabetic Kidney Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Tregs in Autoimmunity: Insights Into Intrinsic Brake Mechanism Driving Pathogenesis and Immune Homeostasis.Frontiers in immunology · 2022Review
- Associations of TP53 codon 72 polymorphism with complications and comorbidities in patients with type 1 diabetes.Journal of molecular medicine (Berlin, Germany) · 2021Article
- eIF5A inhibition influences T cell dynamics in the pancreatic microenvironment of the humanized mouse model of Type 1 Diabetes.Scientific reports · 2019Article
- Targeting Type 1 Diabetes: Selective Approaches for New Therapies.Biochemistry · 2019Review
- Cell Based Therapy for Type 1 Diabetes: Should We Take Hyperglycemia Into Account?Frontiers in immunology · 2019Review
- Memory T Cells in Type 1 Diabetes: the Devil is in the Detail.Current diabetes reports · 2017Review
- Survival of mature T cells in the periphery is intrinsically dependent on GIMAP1 in mice.European journal of immunology · 2017Article
- Increase in Peripheral Blood Intermediate Monocytes is Associated with the Development of Recent-Onset Type 1 Diabetes Mellitus in Children.International journal of biological sciences · 2017Article
- Restoring Regulatory T Cells in Type 1 Diabetes.Current diabetes reports · 2016Review
- Tregs and kidney: From diabetic nephropathy to renal transplantation.World journal of transplantation · 2016Review
- Mechanisms of autoimmunity in the non-obese diabetic mouse: effector/regulatory cell equilibrium during peak inflammation.Immunology · 2016Review
- Treg activation defect in type 1 diabetes: correction with TNFR2 agonism.Clinical & translational immunology · 2016Article
- GIMAP1 Is Essential for the Survival of Naive and Activated B Cells In Vivo.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundType 1 diabetes (T1D) is a T-cell mediated autoimmune disease targeting the insulin-producing pancreatic beta cells. Naturally occurring FOXP3(+)CD4(+)CD25(high) regulatory T cells (T(regs)) play an important role in dominant tolerance, suppressing autoreactive CD4(+) effector T cell activity. Previously, in both recent-onset T1D patients and beta cell antibody-positive at-risk individuals, we observed increased apoptosis and decreased function of polyclonal T(regs) in the periphery. Our objective here was to elucidate the genes and signaling pathways triggering apoptosis in T(regs) from T1D subjects. PRINCIPAL
findingsGene expression profiles of unstimulated T(regs) from recent-onset T1D (n = 12) and healthy control subjects (n = 15) were generated. Statistical analysis was performed using a Bayesian approach that is highly efficient in determining differentially expressed genes with low number of replicate samples in each of the two phenotypic groups. Microarray analysis showed that several cytokine/chemokine receptor genes, HLA genes, GIMAP family genes and cell adhesion genes were downregulated in T(regs) from T1D subjects, relative to control subjects. Several downstream target genes of the AKT and p53 pathways were also upregulated in T1D subjects, relative to controls. Further, expression signatures and increased apoptosis in T(regs) from T1D subjects partially mirrored the response of healthy T(regs) under conditions of IL-2 deprivation. CD4(+) effector T-cells from T1D subjects showed a marked reduction in IL-2 secretion. This could indicate that prior to and during the onset of disease, T(regs) in T1D may be caught up in a relatively deficient cytokine milieu.
conclusionsIn summary, expression signatures in T(regs) from T1D subjects reflect a cellular response that leads to increased sensitivity to apoptosis, partially due to cytokine deprivation. Further characterization of these signaling cascades should enable the detection of genes that can be targeted for restoring T(reg) function in subjects predisposed to T1D.
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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.