biostudies-literatureTzoumpa ALa Caixa FoundationInstituto de Salud Carlos IIINational Research Agency (AEI), Ministry of ScienceGeneralitat Valencianae191354https://www.ebi.ac.uk/biostudies/studies/S-EPMC12487690biostudies-literatureUnknown10(17)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).JCI insightDietary salt intake worsens the Th17-dependent inflammatory profile of patients with cirrhosis.PMC12487690CDEI-03/20-API19/01554,PI22/01907CNS2023-145676LCF/BQ/DI21/11860047GRISOLIAP/2021/083Tzoumpa ARodriguez MHerrera IZapater PMiralles CBellot PMoratalla APomares MTLozano JHuang YPico JGonzalez-Navajas JMLozano-Ruiz BTarin FPinero PPascual SfalseDietary salt intake worsens the Th17-dependent inflammatory profile of patients with cirrhosis.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).2025-01-01T00:00:00Z2025 Sep2026-06-04T01:55:50.807Z2026-05-04T03:14:14.794ZS-EPMC124876904070545410.1172/jci.insight.191354