ArticleThe Journal of clinical investigation2015
Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers, 2 of them syntheses that pooled it.
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
209 citing papers in PubMed, 2 syntheses or guidelines pooled it, 328 citations in OpenAlex.
- Does Sodium Intake Induce Systemic Inflammatory Response? A Systematic Review and Meta-Analysis of Randomized Studies in HumansNutrients · 2021Pooled it
- A Systematic Review of the Impact of Dietary Sodium on Autoimmunity and Inflammation Related to Multiple Sclerosis.Advances in nutrition (Bethesda, Md.) · 2019Pooled it
- Effects of altered salt intake and diet on cytokines in humans: A 20-week randomized cross-over intervention study.European journal of immunology · 2023Trial
- Predictive biomarkers for the efficacy of nivolumab as ≥ 3BMC cancer · 2022Trial
- Exploration of predictors of benefit from nivolumab monotherapy for patients with pretreated advanced gastric and gastroesophageal junction cancer: post hoc subanalysis from the ATTRACTION-2 study.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Trial
- Sodium intake and multiple sclerosis activity and progression in BENEFIT.Annals of neurology · 2017Trial
- High-salt diet in macrophage-associated metabolic disorders: Mechanisms and therapeutic implications.Chinese medical journal · 2026Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Article
- Small RNA Sequencing of Human Urinary Extracellular Vesicles Reveals Association of High-Sodium Diet With Renal Proinflammatory Pathways.Journal of the American Heart Association · 2026Article
- Transcriptomic Analysis Reveals Novel Mechanisms Underlying Neutrophil Activation Induced by High Salt.International journal of molecular sciences · 2026Article
- From high-salt diet to cancer immunity: gut microbiota and immune system interactions and their mechanisms.Frontiers in immunology · 2026Review
- Review
- Blood pressure reduction and anti-inflammatory macrophage augmentation attenuate uterine immune dysregulation and inflammation in mice with salt-sensitive hypertension.Clinical science (London, England : 1979) · 2025Article
- Roles of endothelial cells during infection.Current opinion in immunology · 2025Review
- Dietary Sodium-Potassium Imbalance and Hypertension: Causal Pathways Involving Gut Microbiota Dysbiosis, Inflammation, and Metabolic Disorders.Reviews in cardiovascular medicine · 2025Article
- Dietary salt intake worsens the Th17-dependent inflammatory profile of patients with cirrhosis.JCI insight · 2025Article
- Review
- atRA Attenuates High Salt-Driven EAE Mainly Through Suppressing Th17-Like Regulatory T Cell Response Mediated by the Inhibition of IL-23R Signaling Pathway.Inflammation · 2025Article
- Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential.Biology · 2025Review
149 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
FOXP3+ Tregs are central for the maintenance of self-tolerance and can be defective in autoimmunity. In multiple sclerosis and type-1 diabetes, dysfunctional self-tolerance is partially mediated by a population of IFNγ-secreting Tregs. It was previously reported that increased NaCl concentrations promote the induction of proinflammatory Th17 cells and that high-salt diets exacerbate experimental models of autoimmunity. Here, we have shown that increasing NaCl, either in vitro or in murine models via diet, markedly impairs Treg function. NaCl increased IFNγ secretion in Tregs, and reducing IFNγ - either by neutralization with anti-IFNγ antibodies or shRNA-mediated knockdown - restored suppressive activity in Tregs. The heightened IFNγ secretion and loss of Treg function were mediated by the serum/glucocorticoid-regulated kinase (SGK1). A high-salt diet also impaired human Treg function and was associated with the induction of IFNγ-secreting Tregs in a xenogeneic graft-versus-host disease model and in adoptive transfer models of experimental colitis. Our results demonstrate a putative role for an environmental factor that promotes autoimmunity by inducing proinflammatory responses in CD4 effector cells and Treg pathways.
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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.