ArticlePloS one2016
Comparative Analysis of Protocols to Induce Human CD4+Foxp3+ Regulatory T Cells by Combinations of IL-2, TGF-beta, Retinoic Acid, Rapamycin and Butyrate.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
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Who cites it
72 citing papers in PubMed, 102 citations in OpenAlex.
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- Targeted cellular micropharmacies deliver therapeutic agents to the brain.EMBO molecular medicine · 2026Article
- Rapamycin-modified novel tolerogenic dendritic cells induce liver graft tolerance through MHC-II+CD8+ regulatory T cells.Hepatology communications · 2026Article
- Bioengineered anti-EpCAM-guided exosome nanocarriers delivering Foxp3 agonist butyrate achieve tissue-specific immunomodulation in autoimmune Sjögren's syndrome.Journal of nanobiotechnology · 2026Article
- Review
- TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.Life science alliance · 2026Article
- Immunomodulatory effects of primed amniotic fluid-derived mesenchymal stem/stromal cells with IFN-γ from unexplained recurrent miscarriage sources.Scientific reports · 2026Article
- Regulatory T cell therapy in solid organ transplantation: mechanisms, translational progress, and remaining barriers.Frontiers in immunology · 2026Review
- In Vivo Accumulation of Regulatory T Cells Using Eliglustat-Loaded Cryogels.Advanced healthcare materials · 2025Article
- Article
- ACC1 is a dual metabolic-epigenetic regulator of Treg stability and immune tolerance.Molecular metabolism · 2025Article
- Regenerative Functions of Regulatory T Cells and Current Strategies Utilizing Mesenchymal Stem Cells in Immunomodulatory Tissue Regeneration.Tissue engineering and regenerative medicine · 2025Review
- Harnessing the biology of regulatory T cells to treat disease.Nature reviews. Drug discovery · 2025Review
- Alcohol drinking leads to sex-dependent differentiation of T cells.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025Observational
- Characteristic features ofHeliyon · 2024Article
- PRKAG2.2 is essential for FoxA1Science advances · 2023Article
- Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulatory T cells (Tregs) suppress other immune cells and are critical mediators of peripheral tolerance. Therapeutic manipulation of Tregs is subject to numerous clinical investigations including trials for adoptive Treg transfer. Since the number of naturally occurring Tregs (nTregs) is minute, it is highly desirable to develop a complementary approach of inducing Tregs (iTregs) from naïve T cells. Mouse studies exemplify the importance of peripherally induced Tregs as well as the applicability of iTreg transfer in different disease models. Yet, procedures to generate iTregs are currently controversial, particularly for human cells. Here we therefore comprehensively compare different established and define novel protocols of human iTreg generation using TGF-β in combination with other compounds. We found that human iTregs expressed several Treg signature molecules, such as Foxp3, CTLA-4 and EOS, while exhibiting low expression of the cytokines Interferon-γ, IL-10 and IL-17. Importantly, we identified a novel combination of TGF-β, retinoic acid and rapamycin as a robust protocol to induce human iTregs with superior suppressive activity in vitro compared to currently established induction protocols. However, iTregs generated by these protocols did not stably retain Foxp3 expression and did not suppress in vivo in a humanized graft-versus-host-disease mouse model, highlighting the need for further research to attain stable, suppressive iTregs. These results advance our understanding of the conditions enabling human iTreg generation and may have important implications for the development of adoptive transfer strategies targeting autoimmune and inflammatory diseases.
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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.