ArticleNature medicine2014
Regulatory T cell proliferative potential is impaired in human autoimmune disease.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04294979 (Study on the Interaction Between Immune, Autonomic and Central Nervous Systems as a Target of Exercise Therapy in Multiple Sclerosis), which is not on this map. Cited by 116 papers, 2 of them syntheses that pooled it.
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.
Study on the Interaction Between Immune, Autonomic and Central Nervous Systems as a Target of Exercise Therapy in Multiple Sclerosis
Who cites it
116 citing papers in PubMed, 2 syntheses or guidelines pooled it, 208 citations in OpenAlex.
- The dual role of mTOR in multiple sclerosis pathophysiology: a systematic review.Journal of neurology · 2026Pooled it
- The Role of Selected Interleukins in the Development and Progression of Multiple Sclerosis-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- IL-2 mutein-engrafted antibody MHS552 selectively expands functional regulatory T cells in nonclinical models and healthy participants.Nature communications · 2026Trial
- Cycling CD4+ T cells in HIV-infected immune nonresponders have mitochondrial dysfunction.The Journal of clinical investigation · 2018Trial
- The Footprints of Poly-Autoimmunity: Evidence for Common Biological Factors Involved in Multiple Sclerosis and Hashimoto's Thyroiditis.Frontiers in immunology · 2018Trial
- The Repeated Administration of Resveratrol Has Measurable Effects on Circulating T-Cell Subsets in Humans.Oxidative medicine and cellular longevity · 2017Trial
- The dual role of the PI3K/AKT/mTOR axis in glial cell survival and neuroinflammation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Multiple sclerosis-associated CD226 variant disrupts vitamin D-induced type I Treg differentiation by impairing LFA-1 activation.The Journal of clinical investigation · 2026Article
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Mesenchymal stromal cells and neuroinflammation: a multimodal approach to neuroprotection and future therapeutic horizons.Translational neurodegeneration · 2026Review
- Loss of TET function in T regulatory cells yields ex-Treg cells biased toward T follicular helper cells, causing autoimmune diseases through autoantibody production.Frontiers in immunology · 2026Article
- Treg Susceptibility to Cladribine-Induced Depletion Correlates With Therapy Response in Patients With Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Loss of TET function in T regulatory cells yields ex-Treg cells biased toward T follicular helper cells, causing autoimmune diseases through autoantibody production.bioRxiv : the preprint server for biology · 2025Article
- Review
- The TET-TDG axis in T cells and biological processes.International immunology · 2025Review
- Modulation of NCX1 expression in monocytes associates with multiple sclerosis progression.Heliyon · 2025Article
- Use of regulatory cells for achieving functional tolerance of pig heart xenotransplants in humans: a literature review.Frontiers in immunology · 2025Review
- The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases.Nature reviews. Immunology · 2024Review
- Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?Frontiers in immunology · 2024Review
- Glutaminolysis of CD4Journal of inflammation research · 2024Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Human CD4(+)CD25(high)CD127(-)FoxP3(+) regulatory T (Treg) cells suppress immune responses in vitro and in vivo. Reduced suppressive function and/or number of peripheral Treg cells has been previously reported in autoimmune disorders. Treg cells represent the most actively replicating compartment within the CD4(+) cells in vivo, but they are hyporesponsive to classical T cell receptor (TCR) stimulation in vitro, a condition that is secondary to their overactive metabolic state. Here we report that proliferation of Treg cells after TCR stimulation is impaired in subjects with relapsing-remitting multiple sclerosis (RRMS) because of altered interleukin-2 (IL-2) secretion and IL-2 receptor (IL-2R)-signal transducer and activator of transcription 5 (STAT5) signaling. This is associated with decreased expression of the forkhead box P3 (FoxP3) 44- and 47-kDa splicing forms, overactivation of S6 ribosomal protein (a downstream target of the mammalian target of rapamycin, mTOR) and altered activity of the cyclin-dependent kinase inhibitor p27 (p27(kip1)) and extracellular signal-related kinases 1 and 2 (ERK1/2). The impaired capacity of Treg cells to proliferate in RRMS correlates with the clinical state of the subject, where increasing disease severity is associated with a decline in Treg cell expansion. These results suggest a previously unrecognized mechanism that may account for the progressive loss of Treg cells in autoimmune disease.
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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.