ArticleProceedings of the National Academy of Sciences of the United States of America2014
Interindividual variation in human T regulatory cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- Type 2 Diabetes: How Much of an Autoimmune Disease?Frontiers in endocrinology · 2019Pooled it
- Immune and Metabolic Effects of Antigen-Specific Immunotherapy Using Multiple β-Cell Peptides in Type 1 Diabetes.Diabetes · 2022Trial
- Trial
- Integrating Genetics and Environment to Find Causal Mechanisms for Multiple Sclerosis.European journal of immunology · 2026Review
- Single-cell and multi-omic characterization of ex vivo expanded ASTRLs from stable kidney transplant recipients reveals a regulatory T cell phenotype.Scientific reports · 2026Article
- Oral antigen exposure under costimulation blockade induces Treg cells to establish immune tolerance.The Journal of experimental medicine · 2026Article
- CD25Frontiers in immunology · 2026Article
- Development and validation of a potency assay matrix for optimized and consistent manufacture of clinical mesenchymal stem/stromal cells.Frontiers in immunology · 2026Article
- Pbx1 as a regulator of T-cell fate in autoimmunity.Frontiers in immunology · 2026Review
- Defining nature, responses and drivers of regulatory- and conventional CD4Frontiers in immunology · 2026Article
- Transcriptional fingerprinting of regulatory T cells: ensuring quality in cell therapy applications.Frontiers in immunology · 2025Article
- Development of a humanized mouse model with functional human materno-fetal interface immunity.JCI insight · 2024Article
- An autoimmune transcriptional circuit drives FOXP3Science translational medicine · 2024Article
- The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases.Nature reviews. Immunology · 2024Review
- The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis.Nature communications · 2024Article
- Tregs from human blood differentiate into nonlymphoid tissue-resident effector cells upon TNFR2 costimulation.JCI insight · 2024Article
- Regulatory T-cell dysfunctions are associated with increase in tumor necrosis factor α in autoimmune hemolytic anemia and participate in Th17 polarization.Haematologica · 2024Article
- Identification of human exTNature immunology · 2023Article
- Mutations from patients with IPEX ported to mice reveal different patterns of FoxP3 and Treg dysfunction.Cell reports · 2023Article
- Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen-specific CD4 T cells.Science translational medicine · 2023Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
FOXP3(+) regulatory T (Treg) cells enforce immune self-tolerance and homeostasis, and variation in some aspects of Treg function may contribute to human autoimmune diseases. Here, we analyzed population-level Treg variability by performing genome-wide expression profiling of CD4(+) Treg and conventional CD4(+) T (Tconv) cells from 168 donors, healthy or with established type-1 diabetes (T1D) or type-2 diabetes (T2D), in relation to genetic and immunologic screening. There was a range of variability in Treg signature transcripts, some almost invariant, others more variable, with more extensive variability for genes that control effector function (ENTPD1, FCRL1) than for lineage-specification factors like FOXP3 or IKZF2. Network analysis of Treg signature genes identified coregulated clusters that respond similarly to genetic and environmental variation in Treg and Tconv cells, denoting qualitative differences in otherwise shared regulatory circuits whereas other clusters are coregulated in Treg, but not Tconv, cells, suggesting Treg-specific regulation of genes like CTLA4 or DUSP4. Dense genotyping identified 110 local genetic variants (cis-expression quantitative trait loci), some of which are specifically active in Treg, but not Tconv, cells. The Treg signature became sharper with age and with increasing body-mass index, suggesting a tuning of Treg function with repertoire selection and/or chronic inflammation. Some Treg signature transcripts correlated with FOXP3 mRNA and/or protein, suggesting transcriptional or posttranslational regulatory relationships. Although no single transcript showed significant association to diabetes, overall expression of the Treg signature was subtly perturbed in T1D, but not T2D, patients.
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Registered trials
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.