ArticleThe Journal of experimental medicine2003
Transforming growth factor beta blocks Tec kinase phosphorylation, Ca2+ influx, and NFATc translocation causing inhibition of T cell differentiation.
Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 165 citations in OpenAlex.
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- Revisiting the role of cancer-associated fibroblasts in tumor microenvironment.Frontiers in immunology · 2025Review
- Therapeutic Immunomodulation of Tumor-Lymphatic Crosstalk via Intratumoral Immunotherapy.Molecular pharmaceutics · 2024Review
- TGF-β: an active participant in the immune and metabolic microenvironment of multiple myeloma : TGF-β in the microenvironment of multiple myeloma.Annals of hematology · 2024Review
- Cholesterol sensing and metabolic adaptation in tissue immunity.Trends in immunology · 2024Review
- Oncogenic Calreticulin Induces Immune Escape by Stimulating TGFβ Expression and Regulatory T-cell Expansion in the Bone Marrow Microenvironment.Cancer research · 2024Article
- A pleiotropic recurrent dominantScience advances · 2024Article
- Cancer-associated fibroblasts: a versatile mediator in tumor progression, metastasis, and targeted therapy.Cancer metastasis reviews · 2024Review
- IL-10 and TGF-β, but Not IL-17A or IFN-γ, Potentiate the IL-15-Induced Proliferation of Human T Cells: Association with a Decrease in the Expression of β2m-Free HLA Class I Molecules Induced by IL-15.International journal of molecular sciences · 2024Article
- Biopotency and surrogate assays to validate the immunomodulatory potency of extracellular vesicles derived from mesenchymal stem/stromal cells for the treatment of experimental autoimmune uveitis.Journal of extracellular vesicles · 2024Article
- Defining Human Regulatory T Cells beyond FOXP3: The Need to Combine Phenotype with Function.Cells · 2024Review
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- A novel GPI-anchored dominant-negative TGF-β receptor II renders T cells unresponsive to TGF-β signaling.Molecular therapy oncolytics · 2023Article
- TGF-β broadly modifies rather than specifically suppresses reactivated memory CD8 T cells in a dose-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Steroid receptor coactivator 3 is a key modulator of regulatory T cell-mediated tumor evasion.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Phenotypic plasticity and reduced tissue retention of exhausted tumor-infiltrating T cells following neoadjuvant immunotherapy in head and neck cancer.Cancer cell · 2023Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Transforming growth factor (TGF)-beta inhibits T cell proliferation and differentiation. TGF-beta has been shown to inhibit the expression of transcription factors such as GATA-3 and T-bet that play important roles in T cell differentiation. Here we show that TGF-beta inhibits T cell differentiation at a more proximal step. An early event during T cell activation is increased intracellular calcium levels. Calcium influx in activated T cells and the subsequent activation of transcription factors such as NFATc, events essential for T cell differentiation, are modulated by the Tec kinases that are downstream of the T cell receptor and CD28. We show that in stimulated CD4+ T cells, TGF-beta inhibits phosphorylation and activation of the Tec kinase Itk, increase in intracellular Ca2+ levels, NFATc translocation, and activation of the mitogen-activated protein kinase ERK that together regulate T cell differentiation. Our studies suggest that by inhibiting Itk, and consequently Ca2+ influx, TGF-beta limits T cell differentiation along both the Th1 and Th2 lineages.
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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.