{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tzoumpa A"],"funding":["La Caixa Foundation","Instituto de Salud Carlos III","National Research Agency (AEI), Ministry of Science","Generalitat Valenciana"],"pagination":["e191354"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12487690"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(17)"],"pubmed_abstract":["BACKGROUNDLiver cirrhosis is characterized by chronic inflammation and fibrosis, with Th17 cells playing a crucial role in its progression. Recent evidence suggests that dietary salt influences immune diseases by modulating Th17 differentiation. This study assessed the impact of dietary salt on Th17-driven inflammation in patients with compensated cirrhosis and explored its effects on liver injury in mouse models.METHODSA nondrug, open-label, nonrandomized study involved 37 patients with compensated cirrhosis, who were given personalized guidelines to reduce salt intake over 3 months. Changes in Th17-driven inflammation and liver function markers were assessed at baseline and after salt restriction. In parallel, the impact of a high-salt diet on hepatic CD4+ T cells was analyzed in mouse models of acute liver injury and fibrosis.RESULTSHigh salt intake was associated with Th17-mediated inflammation and correlated with markers of impaired liver function in these patients. Importantly, moderating salt intake through a personalized nutritional intervention was sufficient to reduce CD4+ T cell-mediated inflammation. Furthermore, analysis of RNA-seq data revealed enrichment of salt-induced Th17 gene signatures in both liver tissue and peripheral cells from patients with liver disease. Similarly, mice fed a high salt diet showed hepatic enrichment of Th17 cells and exacerbated liver fibrosis upon injury. Mechanistic studies revealed that high sodium conditions activated NF-κB and induced IL-6 production in hepatocytes, which may promote Th17 responses.CONCLUSIONDietary salt exacerbates Th17-driven inflammation and contributes to cirrhosis progression. Salt reduction may represent a viable therapeutic approach to manage inflammation in compensated cirrhosis.FUNDINGGrants PI19/01554 and PI22/01907 from Instituto de Salud Carlos III (Madrid, Spain), CDEI-03/20-A and CIPROM/2023/4 from Generalitat Valenciana (Valencia, Spain), CNS2023-145676 from the National Research Agency (AEI) (Madrid, Spain), and LCF/BQ/D121/11860047 from La Caixa Foundation (Barcelona, Spain)."],"journal":["JCI insight"],"pubmed_title":["Dietary salt intake worsens the Th17-dependent inflammatory profile of patients with cirrhosis."],"pmcid":["PMC12487690"],"funding_grant_id":["CDEI-03/20-A","PI19/01554,PI22/01907","CNS2023-145676","LCF/BQ/DI21/11860047","GRISOLIAP/2021/083"],"pubmed_authors":["Tzoumpa A","Rodriguez M","Herrera I","Zapater P","Miralles C","Bellot P","Moratalla A","Pomares MT","Lozano J","Huang Y","Pico J","Gonzalez-Navajas JM","Lozano-Ruiz B","Tarin F","Pinero P","Pascual S"],"additional_accession":[]},"is_claimable":false,"name":"Dietary salt intake worsens the Th17-dependent inflammatory profile of patients with cirrhosis.","description":"BACKGROUNDLiver cirrhosis is characterized by chronic inflammation and fibrosis, with Th17 cells playing a crucial role in its progression. Recent evidence suggests that dietary salt influences immune diseases by modulating Th17 differentiation. This study assessed the impact of dietary salt on Th17-driven inflammation in patients with compensated cirrhosis and explored its effects on liver injury in mouse models.METHODSA nondrug, open-label, nonrandomized study involved 37 patients with compensated cirrhosis, who were given personalized guidelines to reduce salt intake over 3 months. Changes in Th17-driven inflammation and liver function markers were assessed at baseline and after salt restriction. In parallel, the impact of a high-salt diet on hepatic CD4+ T cells was analyzed in mouse models of acute liver injury and fibrosis.RESULTSHigh salt intake was associated with Th17-mediated inflammation and correlated with markers of impaired liver function in these patients. Importantly, moderating salt intake through a personalized nutritional intervention was sufficient to reduce CD4+ T cell-mediated inflammation. Furthermore, analysis of RNA-seq data revealed enrichment of salt-induced Th17 gene signatures in both liver tissue and peripheral cells from patients with liver disease. Similarly, mice fed a high salt diet showed hepatic enrichment of Th17 cells and exacerbated liver fibrosis upon injury. Mechanistic studies revealed that high sodium conditions activated NF-κB and induced IL-6 production in hepatocytes, which may promote Th17 responses.CONCLUSIONDietary salt exacerbates Th17-driven inflammation and contributes to cirrhosis progression. Salt reduction may represent a viable therapeutic approach to manage inflammation in compensated cirrhosis.FUNDINGGrants PI19/01554 and PI22/01907 from Instituto de Salud Carlos III (Madrid, Spain), CDEI-03/20-A and CIPROM/2023/4 from Generalitat Valenciana (Valencia, Spain), CNS2023-145676 from the National Research Agency (AEI) (Madrid, Spain), and LCF/BQ/D121/11860047 from La Caixa Foundation (Barcelona, Spain).","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-04T01:55:50.807Z","creation":"2026-05-04T03:14:14.794Z"},"accession":"S-EPMC12487690","cross_references":{"pubmed":["40705454"],"doi":["10.1172/jci.insight.191354"]}}