ArticlePLoS biology2013
TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 101 citations in OpenAlex.
- Advances in nucleotide-based P2Y₁ antagonism: implications for cardiovascular therapeutics.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- TGF-β and IL-2 differentially shape T follicular regulatory cell differentiation and stability in vitro.Cellular & molecular immunology · 2026Article
- HIF-1αImmunity · 2026Article
- Spontaneous somatic Pten loss contributes to functional heterogeneity of T cells.Scientific reports · 2026Article
- Identification of a neoplastic Tfh-like cellular subset in a mouse model of angioimmunoblastic T cell lymphoma.Frontiers in oncology · 2026Article
- Temporal and context-dependent requirements for the transcription factor Foxp3 expression in regulatory T cells.Nature immunology · 2025Article
- Heterogeneity of thymic output in the elderly and its association with sex and smoking.JCI insight · 2025Article
- Therapeutic targeting of TGF-β in lung cancer.The FEBS journal · 2025Review
- Differential regulation of Treg stability in human naïve and effector Treg subsets by TGFβ-signaling via ARKADIA-SKI axis.Frontiers in immunology · 2025Article
- Refined tamoxifen administration in mice by encouraging voluntary consumption of palatable formulations.Lab animal · 2024Article
- The dynamics and longevity of circulating CD4+ memory T cells depend on cell age and not the chronological age of the host.PLoS biology · 2024Article
- The dynamics and longevity of circulating CD4bioRxiv : the preprint server for biology · 2024Article
- The IL-17 family in diseases: from bench to bedside.Signal transduction and targeted therapy · 2023Review
- Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging.Nature immunology · 2023Article
- TGFβ control of immune responses in cancer: a holistic immuno-oncology perspective.Nature reviews. Immunology · 2023Review
- B cell- and T cell-intrinsic regulation of germinal centers by thymic stromal lymphopoietin signaling.Science immunology · 2023Article
- The roles of TGF-β and VEGF pathways in the suppression of antitumor immunity in melanoma and other solid tumors.Pharmacology & therapeutics · 2022Review
- The function of Wtap in NNature immunology · 2022Article
- Breast cancer cell-derived extracellular vesicles promote CD8Nature communications · 2022Article
- Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells.Immunity · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β is widely held to be critical for the maintenance and function of regulatory T (T(reg)) cells and thus peripheral tolerance. This is highlighted by constitutive ablation of TGF-β receptor (TR) during thymic development in mice, which leads to a lethal autoimmune syndrome. Here we describe that TGF-β-driven peripheral tolerance is not regulated by TGF-β signalling on mature CD4⁺ T cells. Inducible TR2 ablation specifically on CD4⁺ T cells did not result in a lethal autoinflammation. Transfer of these TR2-deficient CD4⁺ T cells to lymphopenic recipients resulted in colitis, but not overt autoimmunity. In contrast, thymic ablation of TR2 in combination with lymphopenia led to lethal multi-organ inflammation. Interestingly, deletion of TR2 on mature CD4⁺ T cells does not result in the collapse of the T(reg) cell population as observed in constitutive models. Instead, a pronounced enlargement of both regulatory and effector memory T cell pools was observed. This expansion is cell-intrinsic and seems to be caused by increased T cell receptor sensitivity independently of common gamma chain-dependent cytokine signals. The expression of Foxp3 and other regulatory T cells markers was not dependent on TGF-β signalling and the TR2-deficient T(reg) cells retained their suppressive function both in vitro and in vivo. In summary, absence of TGF-β signalling on mature CD4⁺ T cells is not responsible for breakdown of peripheral tolerance, but rather controls homeostasis of mature T cells in adult mice.
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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.