ArticleThe Journal of clinical investigation2020
Salt generates antiinflammatory Th17 cells but amplifies pathogenicity in proinflammatory cytokine microenvironments.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- SGK1 inhibition supports neuroprotection in spinal cord injury by suppressing oxidative stress and AIM2 activation via FoxO1 mediated mitophagy.Journal of neuroinflammation · 2026Article
- Development and validation of nomograms integrating electrolyte, nutritional, and inflammatory indicators to predict survival in advanced esophageal cancer undergoing immunotherapy or radioimmunotherapy.Journal of thoracic disease · 2026Article
- High-salt diet aggravates allergic rhinitis through the NFAT5 signaling pathway.NPJ science of food · 2026Article
- Fructose intake driven glycolysis-ROS-EGFR axis specifically promotes the generation and pathogenicity of Th17 cells.Nature communications · 2025Article
- Metabolic Stress Expands Polyfunctional, Proinflammatory ThArthritis & rheumatology (Hoboken, N.J.) · 2025Article
- High-salt-driven gut microbiota dysfunction aggravates prostatitis by promoting AHR/SGK1/FOXO1 axis-mediated Th17 cell differentiation.Military Medical Research · 2025Article
- Aryl Hydrocarbon Receptor Activation Promotes Effector CD4+ T Cell Homeostasis and Restrains Salt-Sensitive Hypertension.Function (Oxford, England) · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- The immune-microbiome axis in salt-sensitive hypertension: a focus on renal and neural mechanisms.Frontiers in physiology · 2025Review
- Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity.Nature immunology · 2024Article
- NaCl enhances CD8Nature immunology · 2024Article
- Akkermansia muciniphila extracellular vesicles have a protective effect against hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Simultaneous Increases in Intracellular Sodium and Tonicity Boost Antimicrobial Activity of Macrophages.Cells · 2023Article
- Hypertonic Salt Solution Enhances Inflammatory Responses in Cultured Splenic T-Cells from Dahl Salt-Sensitive Rats but Not Dahl Salt-Resistant Rats.Journal of cardiovascular development and disease · 2023Article
- Role of Serum/Glucocorticoid-Regulated Kinase 1 (SGK1) in Immune and Inflammatory Diseases.Inflammation · 2023Review
- T helper cell polarity determines salt sensitivity and hypertension development.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Paracellular permeability and tight junction regulation in gut health and disease.Nature reviews. Gastroenterology & hepatology · 2023Review
- An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza.Communications biology · 2023Article
- Article
- Long Noncoding RNA U90926 Is Induced in Activated Macrophages, Is Protective in Endotoxic Shock, and Encodes a Novel Secreted Protein.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
Corrections and comments
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Authors and funding
18 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Th cells integrate signals from their microenvironment to acquire distinct specialization programs for efficient clearance of diverse pathogens or for immunotolerance. Ionic signals have recently been demonstrated to affect T cell polarization and function. Sodium chloride (NaCl) was proposed to accumulate in peripheral tissues upon dietary intake and to promote autoimmunity via the Th17 cell axis. Here, we demonstrate that high-NaCl conditions induced a stable, pathogen-specific, antiinflammatory Th17 cell fate in human T cells in vitro. The p38/MAPK pathway, involving NFAT5 and SGK1, regulated FoxP3 and IL-17A expression in high-NaCl conditions. The NaCl-induced acquisition of an antiinflammatory Th17 cell fate was confirmed in vivo in an experimental autoimmune encephalomyelitis (EAE) mouse model, which demonstrated strongly reduced disease symptoms upon transfer of T cells polarized in high-NaCl conditions. However, NaCl was coopted to promote murine and human Th17 cell pathogenicity, if T cell stimulation occurred in a proinflammatory and TGF-β-low cytokine microenvironment. Taken together, our findings reveal a context-dependent, dichotomous role for NaCl in shaping Th17 cell pathogenicity. NaCl might therefore prove beneficial for the treatment of chronic inflammatory diseases in combination with cytokine-blocking drugs.
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