ArticleJournal of immunology (Baltimore, Md. : 1950)2014
TGF-β-mediated Foxp3 gene expression is cooperatively regulated by Stat5, Creb, and AP-1 through CNS2.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 86 citations in OpenAlex.
- TGF-β-induced Tregs release extracellular vesicles that modulate CD4+ T-cell proliferation and phenotype in a Nrp1-dependent manner.ImmunoHorizons · 2026Article
- Review
- IL-6 as a central driver of immune evasion in PDAC: from IDO-mediated tolerance to multi-pathway immunosuppression.Frontiers in immunology · 2026Review
- Beyond Foxp3 and TSDR: a dual epigenetic lock framework for treg stability and plasticity.Frontiers in immunology · 2026Review
- Differential regulation of Treg stability in human naïve and effector Treg subsets by TGFβ-signaling via ARKADIA-SKI axis.Frontiers in immunology · 2025Article
- Early Growth Response Gene 1 Benefits Autoimmune Disease by Promoting Regulatory T Cell Differentiation as a Regulator of Foxp3.Research (Washington, D.C.) · 2025Article
- Bioactive peptides and proteins for tissue repair: microenvironment modulation, rational delivery, and clinical potential.Military Medical Research · 2024Review
- Oral administration of Lactobacillus plantarum expressing aCD11c modulates cellular immunity alleviating inflammatory injury due to Klebsiella pneumoniae infection.BMC veterinary research · 2024Article
- Deciphering the role of protein kinase A in the control of FoxP3 expression in regulatory T cells in health and autoimmunity.Scientific reports · 2024Article
- The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient "Yin-Yang" theory and modern immunology.Cell communication and signaling : CCS · 2024Review
- Deciphering the developmental trajectory of tissue-resident Foxp3Frontiers in immunology · 2024Review
- Decoding mutational hotspots in human disease through the gene modules governing thymic regulatory T cells.Frontiers in immunology · 2024Article
- Ageing and Low-Level Chronic Inflammation: The Role of the Biological Clock.Antioxidants (Basel, Switzerland) · 2022Review
- The ADP-Ribosylation Factor 4d Restricts Regulatory T-Cell Induction via Control of IL-2 Availability.Cells · 2022Article
- Transforming growth factor-β1 in regulatory T cell biology.Science immunology · 2022Review
- Role of CNSs Conserved Distal Cis-Regulatory Elements in CD4 + T Cell Development and Differentiation.Frontiers in immunology · 2022Review
- Genetic Variations Controlling Regulatory T Cell Development and Activity in Mouse Models of Lupus-Like Autoimmunity.Frontiers in immunology · 2022Review
- Bone Morphogenetic Proteins Shape TFrontiers in immunology · 2022Review
- MiR-210-5p regulates STAT3 activation by targeting STAT5A in the differentiation of dermal fibroblasts.3 Biotech · 2021Article
- SPRC Suppresses Experimental Periodontitis by Modulating Th17/Treg Imbalance.Frontiers in bioengineering and biotechnology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Foxp3 plays an important role in the development and the function of regulatory T cells (Treg). Both the induction and maintenance of Foxp3 gene expression are controlled by several regulatory regions including two enhancers in the conserved noncoding sequences (CNS). The functions of Enhancer 1 in CNS1 are well established, whereas those of Enhancer 2 in CNS2 remain unclear. Although CNS2 contains enhancer activity, methylated CpG sequences in this region prevent Foxp3 gene expression in Foxp3(-) T cells. These sequences are, however, demethylated in Foxp3(+) Treg by mechanisms as yet unknown. To investigate the role of CNS2, we have determined the Enhancer 2 core sequence by luciferase reporter assays in the absence of methylation to exclude the inhibitory effect and shown that transcription factors AP-1, Stat5, and Creb cooperate in regulating Enhancer 2 activity. We have then determined the methylation sensitivity of each of the transcription factors. AP-1 was found to be methylation sensitive as has previously been described for Creb. However, Stat5 was active even when its binding site in CNS2 was methylated. Stat5 binding to Enhancer 2 occurred early and preceded that of AP-1 and Creb during Treg induction. In addition, Stat5 activation is itself dependent on TGF-β signaling through Smad3-mediated blockade of Socs3 expression. These findings suggest that Stat5 is a key regulator for opening up the CNS2 region during induced Treg induction, whereas AP-1 and Creb maintain Enhancer 2 activity.
Indexed as
Identifiers
What OpenQuestion holds
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.