ArticlePloS one2011
All-trans retinoic acid promotes TGF-β-induced Tregs via histone modification but not DNA demethylation on Foxp3 gene locus.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 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
74 citing papers in PubMed, 111 citations in OpenAlex.
- Regulatory T cells in axial spondyloarthritis.Communications biology · 2026Review
- ACC1 is a dual metabolic-epigenetic regulator of Treg stability and immune tolerance.Molecular metabolism · 2025Article
- T-regulatory cells for the treatment of autoimmune diseases.Frontiers in immunology · 2025Review
- Augmenting regulatory T cells: new therapeutic strategy for rheumatoid arthritis.Frontiers in immunology · 2024Review
- Expression characteristics of peripheral lymphocyte programmed death 1 and FoxP3World journal of gastroenterology · 2023Article
- Downregulation of chemokine receptor 9 facilitates CD4Nature communications · 2023Article
- Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy.Biomedicines · 2023Review
- Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- BNIP-2 Activation of Cellular Contractility Inactivates YAP for H9c2 Cardiomyoblast Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Transforming growth factor-β1 in regulatory T cell biology.Science immunology · 2022Review
- Functional Diversities of Regulatory T Cells in the Context of Cancer Immunotherapy.Frontiers in immunology · 2022Review
- Autoimmunity and Cancer-Two Sides of the Same Coin.Frontiers in immunology · 2022Review
- Role of CNSs Conserved Distal Cis-Regulatory Elements in CD4 + T Cell Development and Differentiation.Frontiers in immunology · 2022Review
- TGF-β-induced CD4+ FoxP3+ regulatory T cell-derived extracellular vesicles modulate Notch1 signaling through miR-449a and prevent collagen-induced arthritis in a murine model.Cellular & molecular immunology · 2021Article
- Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment.Cancer immunology, immunotherapy : CII · 2021Review
- Regulatory T Cells-Related Genes Are under DNA Methylation Influence.International journal of molecular sciences · 2021Review
- On the Role of Salt in Immunoregulation and Autoimmunity.Mediterranean journal of rheumatology · 2021Article
- Ubiquitin-Dependent Regulation of Treg Function and Plasticity.Advances in experimental medicine and biology · 2021Article
- Diet and Hygiene in Modulating Autoimmunity During the Pandemic Era.Frontiers in immunology · 2021Review
- Regulatory T Cells in Autoimmunity and Cancer: A Duplicitous Lifestyle.Frontiers in immunology · 2021Review
14 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
16 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundIt has been documented all-trans retinoic acid (atRA) promotes the development of TGF-β-induced CD4(+)Foxp3(+) regulatory T cells (iTreg) that play a vital role in the prevention of autoimmune responses, however, molecular mechanisms involved remain elusive. Our objective, therefore, was to determine how atRA promotes the differentiation of iTregs. METHODOLOGY/PRINCIPAL
findingsAddition of atRA to naïve CD4(+)CD25(-) cells stimulated with anti-CD3/CD28 antibodies in the presence of TGF-β not only increased Foxp3(+) iTreg differentiation, but maintained Foxp3 expression through apoptosis inhibition. atRA/TGF-β-treated CD4(+) cells developed complete anergy and displayed increased suppressive activity. Infusion of atRA/TGF-β-treated CD4(+) cells resulted in the greater effects on suppressing symptoms and protecting the survival of chronic GVHD mice with typical lupus-like syndromes than did CD4(+) cells treated with TGF-β alone. atRA did not significantly affect the phosphorylation levels of Smad2/3 and still promoted iTreg differentiation in CD4(+) cells isolated from Smad3 KO and Smad2 conditional KO mice. Conversely, atRA markedly increased ERK1/2 activation, and blockade of ERK1/2 signaling completely abolished the enhanced effects of atRA on Foxp3 expression. Moreover, atRA significantly increased histone methylation and acetylation within the promoter and conserved non-coding DNA sequence (CNS) elements at the Foxp3 gene locus and the recruitment of phosphor-RNA polymerase II, while DNA methylation in the CNS3 was not significantly altered. CONCLUSIONS/SIGNIFICANCE: We have identified the cellular and molecular mechanism(s) by which atRA promotes the development and maintenance of iTregs. These results will help to enhance the quantity and quality of development of iTregs and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation.
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.