ArticleEMBO reports2016
AKT isoforms modulate Th1-like Treg generation and function in human autoimmune disease.
Article in EMBO reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 68 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
68 citing papers in PubMed, 107 citations in OpenAlex.
- GPCR-Driven Muscarinic M1 and Histamine H1 Receptor Signaling Converging on the PI3K/Akt/mTOR Pathway: Functional Integration in Neuroinflammation and Myelin Repair in Multiple Sclerosis.Molecular neurobiology · 2026Review
- Computational identification and experimental validation of shared diagnostic biomarkers and gene signatures across HLA-B27-associated immune-mediated diseases.Journal of translational medicine · 2026Article
- T-betThe FEBS journal · 2026Article
- A loss of the cytosolic branched-chain aminotransferase, BCATc, enhances TImmunometabolism (Cobham, Surrey) · 2026Article
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- PMEPA1-Mediated Treg Cell Impairment Promotes Endometrial Stromal Invasion via Excessive PI3K/AKT Signaling in Endometriosis.Current medical science · 2025Article
- Article
- Differential regulation of calcium-NFAT signaling pathway by Akt isoforms: unraveling effector dynamics and exhaustion of cytotoxic T lymphocytes in tumor microenvironment.Journal for immunotherapy of cancer · 2025Article
- Anti-PD-1 amplifies costimulation in melanoma-infiltrating TJournal for immunotherapy of cancer · 2025Article
- Sphingosine-1-Phosphate Signalling Inhibition Suppresses Th1-Like Treg Generation by Reversing Mitochondrial Uncoupling.Immunology · 2025Article
- Breaking tolerance: the autoimmune aspect of atherosclerosis.Nature reviews. Immunology · 2024Review
- The role of regulatory T cells in vitiligo and therapeutic advances: a mini-review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Complex Role of Regulatory T Cells (Tregs) in the Tumor Microenvironment: Their Molecular Mechanisms and Bidirectional Effects on Cancer Progression.International journal of molecular sciences · 2024Review
- The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases.Nature reviews. Immunology · 2024Review
- Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions.Signal transduction and targeted therapy · 2024Review
- CRIF1 deficiency induces FOXP3Science advances · 2024Article
- Treg plasticity and human diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Lung tumor-infiltrating TScience immunology · 2023Article
- Article
- Immunomodulatory actions of vitamin D in various immune-related disorders: a comprehensive review.Frontiers in immunology · 2023Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Foxp3(+) regulatory T cells (Tregs) exhibit plasticity, which dictates their function. Secretion of the inflammatory cytokine IFNγ, together with the acquisition of a T helper 1 (Th1)-like effector phenotype as observed in cancer, infection, and autoimmune diseases, is associated with loss of Treg suppressor function through an unknown mechanism. Here, we describe the signaling events driving the generation of human Th1-Tregs. Using a genome-wide gene expression approach and pathway analysis, we identify the PI3K/AKT/Foxo1/3 signaling cascade as the major pathway involved in IFNγ secretion by human Tregs. Furthermore, we describe the opposing roles of AKT isoforms in Th1-Treg generation ex vivo Finally, we employ multiple sclerosis as an in vivo model with increased but functionally defective Th1-Tregs. We show that the PI3K/AKT/Foxo1/3 pathway is activated in ex vivo-isolated Tregs from untreated relapsing-remitting MS patients and that blockade of the pathway inhibits IFNγ secretion and restores the immune suppressive function of Tregs. These data define a fundamental pathway regulating the function of human Tregs and suggest a novel treatment paradigm for autoimmune diseases.
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.