ArticleThe Journal of experimental medicine2008
The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells.
Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 431 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
431 citing papers in PubMed, 1 synthesis or guideline pooled it, 714 citations in OpenAlex.
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- Sex Steroid Hormone Regulation of T-Cell Function and Antitumor Immunity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Phase I Trial of Ipatasertib plus Atezolizumab Enhances PI3K/AKT Pathway Immune Responses in Solid Tumors and Refractory Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.Life science alliance · 2026Article
- Metabolic checkpoints in the regulation of Th17 cells: implications for uveitis pathogenesis and therapy.Frontiers in immunology · 2026Review
- Unveiling natural anti-inflammatory compounds for sinusitis treatments by modulating FOXP3, C5aR1, and LIF.Frontiers in immunology · 2026Review
- Sirolimus for the treatment of Graves' orbitopathy.Thyroid research · 2025Review
- Evolutionary Dynamics of Oncosuppression Under Selection Pressure.Life (Basel, Switzerland) · 2025Article
- Metabolic regulation of Th17 and Treg cell balance by the mTOR signaling.Metabolism open · 2025Review
- Inflammation and cancer cell survival: TRAF2 as a key player.Cell death & disease · 2025Review
- The Kynurenine Pathway and Indole Pathway in Tryptophan Metabolism Influence Tumor Progression.Cancer medicine · 2025Review
- Influences of metabolism and lipid homeostasis on regulatory vs. conventional T cells and implications for autoimmunity.Frontiers in immunology · 2025Review
- Deciphering the deterministic role of TCR signaling in T cell fate determination.Frontiers in immunology · 2025Review
- ICI-induced cardiovascular toxicity: mechanisms and immune reprogramming therapeutic strategies.Frontiers in immunology · 2025Review
- HnRNP L is essential for peripheral T cell proliferation and survival.Frontiers in immunology · 2025Article
- Metabolic targeting of regulatory T cells in oral squamous cell carcinoma: new horizons in immunotherapy.Molecular cancer · 2024Review
371 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
CD4(+)Foxp3(+) regulatory T (T reg) cells play an essential role in maintaining immunological tolerance via their suppressive function on conventional CD4(+) T (Tconv) cells. Repertoire studies suggest that distinct T cell receptor signaling pathways lead to T reg differentiation, but the signals that regulate T reg specification are largely unknown. We identify AKT as a strong repressor of entry into the T reg phenotype in vitro and in vivo. A constitutively active allele of AKT substantially diminished TGF-beta-induced Foxp3 expression in a kinase-dependent manner and via a rapamycin-sensitive pathway, implicating the AKT-mammalian target of rapamycin axis. The observed impairment in Foxp3 induction was part of a broad dampening of the typical T reg transcriptional signature. Expression of active AKT at a stage before Foxp3 turn on during normal T reg differentiation in the thymus selectively impaired differentiation of CD4(+)Foxp3(+) cells without any alteration in the positive selection of Tconv. Activated AKT, in contrast, did not affect established Foxp3 expression in T reg cells. These results place AKT at a nexus of signaling pathways whose proper activation has a strong and broad impact on the onset of T reg specification.
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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.