ArticleEuropean journal of immunology2011
TGF-β signaling via Smad4 drives IL-10 production in effector Th1 cells and reduces T-cell trafficking in EAE.
Article in European journal of immunology, 2011. 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 31 papers.
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
31 citing papers in PubMed, 48 citations in OpenAlex.
- The antiepileptic drug valproic acid restores T cell homeostasis and ameliorates pathogenesis of experimental autoimmune encephalomyelitis.The Journal of biological chemistry · 2012Trial
- A microRNA atlas of CD4+ T cell subsets in experimental autoimmune encephalomyelitis identifies regulators of disease pathogenesis.PLoS biology · 2026Article
- An Update on Dynamic Changes in Cytokine Expression and Dysbiosis Due to Radiation Combined Injury.International journal of molecular sciences · 2025Review
- SMAD4 enhances the cytotoxic efficacy of human NK cells against colorectal cancer cells via the mFrontiers in immunology · 2024Article
- Vitamin D as a Risk Factor for Multiple Sclerosis: Immunoregulatory or Neuroprotective?Frontiers in neurology · 2022Review
- IL-10 in glioma.British journal of cancer · 2021Review
- Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice.Journal of translational medicine · 2021Article
- Consequences of Mutations and Abnormal Expression of SMAD4 in Tumors and T Cells.OncoTargets and therapy · 2021Review
- The induction and function of the anti-inflammatory fate of TNature communications · 2020Article
- The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives.PloS one · 2020Article
- COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm.Oxidative medicine and cellular longevity · 2020Review
- Molecular switches for regulating the differentiation of inflammatory and IL-10-producing anti-inflammatory T-helper cells.Cellular and molecular life sciences : CMLS · 2020Review
- The rs3761548 FOXP3 variant is associated with multiple sclerosis and transforming growth factor β1 levels in female patients.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Article
- Interleukin 17 (IL-17)-Induced Mesenchymal Stem Cells Prolong the Survival of Allogeneic Skin Grafts.Annals of transplantation · 2018Article
- Integrative analysis of Multiple Sclerosis using a systems biology approach.Scientific reports · 2018Article
- Conjugation of Transforming Growth Factor Beta to Antigen-Loaded Poly(lactide- co-glycolide) Nanoparticles Enhances Efficiency of Antigen-Specific Tolerance.Bioconjugate chemistry · 2018Article
- Cutaneous leukocytoclastic vasculitis: the role of lymphocytes and related immune markers.Postepy dermatologii i alergologii · 2017Article
- A Functional Variant of SMAD4 Enhances Thoracic Aortic Aneurysm and Dissection Risk through Promoting Smooth Muscle Cell Apoptosis and Proteoglycan Degradation.EBioMedicine · 2017Article
- TGF-β regulation of encephalitogenic and regulatory T cells in multiple sclerosis.European journal of immunology · 2017Review
- Lamina Propria CD4+LAP+ Regulatory T Cells Are Increased in Active Ulcerative Colitis but Show Increased IL-17 Expression and Reduced Suppressor Activity.Journal of Crohn's & colitis · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Effector Th1 cells perpetuate inflammatory damage in a number of autoimmune diseases, including MS and its animal model EAE. Recently, a self-regulatory mechanism was described in which effector Th1 cells produce the immunomodulatory cytokine IL-10 to dampen the inflammatory response in both normal and autoimmune inflammation. While the presence of TGF-β has been suggested to enhance and stabilize an IFN-γ(+) IL-10(+) phenotype, the molecular mechanism is poorly understood. Additionally, in the context of adoptive transfer EAE, it is unclear whether IL-10 acts on the transferred Th1 cells or on endogenous host cells. In the present study, using myelin-specific TCR-Tg mice, we show that repetitive Ag stimulation of effector Th1 cells in the presence of TGF-β increases the population of IFN-γ(+) IL-10(+) cells, which correlates with a decrease in EAE severity. Additionally, TGF-β signaling causes binding of Smad4 to the IL-10 promoter, providing molecular evidence for TGF-β-mediated IL-10 production from Th1 effector cells. Finally, this study demonstrates that IL-10 not only reduces encephalitogenic markers such as IFN-γ and T-bet on Th1 effector cells expressing the IL-10R but also prevents recruitment of both transferred and host-derived inflammatory T cells. These data establish a regulatory mechanism by which highly activated Th1 effector cells modulate their pathogenicity through the induction of IL-10.
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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.