Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model

Abstract Although the immune system plays a crucial role in hypertension, its underlying mechanisms remain unclear. While extensive research has explored the gut-immune relationship in various diseases, the role of gut immunity in salt-sensitive (SS) hypertension is not well understood. In this stud...

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Main Authors: Sung Yong Joo, Sang Jin Lee, Seung Jun Lee, Su Ah Seo, Cheong-Wun Kim, Su-Hyung Hong, InKyeom Kim, Myunghoo Kim
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-11100-z
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author Sung Yong Joo
Sang Jin Lee
Seung Jun Lee
Su Ah Seo
Cheong-Wun Kim
Su-Hyung Hong
InKyeom Kim
Myunghoo Kim
author_facet Sung Yong Joo
Sang Jin Lee
Seung Jun Lee
Su Ah Seo
Cheong-Wun Kim
Su-Hyung Hong
InKyeom Kim
Myunghoo Kim
author_sort Sung Yong Joo
collection DOAJ
description Abstract Although the immune system plays a crucial role in hypertension, its underlying mechanisms remain unclear. While extensive research has explored the gut-immune relationship in various diseases, the role of gut immunity in salt-sensitive (SS) hypertension is not well understood. In this study, we aimed to elucidate the role of gut immunity in the development of SS hypertension by analyzing immune cells in the gut and blood using single-cell RNA sequencing (scRNA-seq). Six-week-old Dahl SS rats were fed either a normal salt diet (NSD; 0.4% NaCl) or a high-salt diet (HSD; 4% NaCl) for four weeks. Blood pressure was measured weekly using the tail-cuff method. After four weeks, small intestine lamina propria cells (SILPs) and peripheral blood mononuclear cells (PBMCs) were isolated and subjected to scRNA-seq. Our results demonstrated an increase in gut B and T follicular helper (Tfh)-like cells in SS rats. Furthermore, KEGG pathway analysis revealed that HSD upregulated IL-6 receptor (IL-6R)-JAK-STAT signaling in B cells and Tfh-like cells. These findings provide novel insights into the potential of targeting the gut immunity in the treatment of SS hypertension.
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spelling doaj-art-369869f7fa664f1ba18a78256f7cbcf32025-08-24T11:26:13ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-11100-zSingle-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal modelSung Yong Joo0Sang Jin Lee1Seung Jun Lee2Su Ah Seo3Cheong-Wun Kim4Su-Hyung Hong5InKyeom Kim6Myunghoo Kim7Department of Animal Science, College of Natural Resources & Life Science, Pusan National UniversityCardiovascular Research Institute, School of Medicine, Kyungpook National UniversityDepartment of Animal Science, College of Natural Resources & Life Science, Pusan National UniversityDepartment of Animal Science, College of Natural Resources & Life Science, Pusan National UniversityCardiovascular Research Institute, School of Medicine, Kyungpook National UniversityDepartment of Microbiology and Immunology, School of Dentistry, Kyungpook National UniversityCardiovascular Research Institute, School of Medicine, Kyungpook National UniversityDepartment of Animal Science, College of Natural Resources & Life Science, Pusan National UniversityAbstract Although the immune system plays a crucial role in hypertension, its underlying mechanisms remain unclear. While extensive research has explored the gut-immune relationship in various diseases, the role of gut immunity in salt-sensitive (SS) hypertension is not well understood. In this study, we aimed to elucidate the role of gut immunity in the development of SS hypertension by analyzing immune cells in the gut and blood using single-cell RNA sequencing (scRNA-seq). Six-week-old Dahl SS rats were fed either a normal salt diet (NSD; 0.4% NaCl) or a high-salt diet (HSD; 4% NaCl) for four weeks. Blood pressure was measured weekly using the tail-cuff method. After four weeks, small intestine lamina propria cells (SILPs) and peripheral blood mononuclear cells (PBMCs) were isolated and subjected to scRNA-seq. Our results demonstrated an increase in gut B and T follicular helper (Tfh)-like cells in SS rats. Furthermore, KEGG pathway analysis revealed that HSD upregulated IL-6 receptor (IL-6R)-JAK-STAT signaling in B cells and Tfh-like cells. These findings provide novel insights into the potential of targeting the gut immunity in the treatment of SS hypertension.https://doi.org/10.1038/s41598-025-11100-z
spellingShingle Sung Yong Joo
Sang Jin Lee
Seung Jun Lee
Su Ah Seo
Cheong-Wun Kim
Su-Hyung Hong
InKyeom Kim
Myunghoo Kim
Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model
Scientific Reports
title Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model
title_full Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model
title_fullStr Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model
title_full_unstemmed Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model
title_short Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model
title_sort single cell rna sequencing reveals that a high salt diet increases il6r jak1 stat3 gene signaling pathway activity in intestinal b cells and tfh cells of salt sensitive hypertension animal model
url https://doi.org/10.1038/s41598-025-11100-z
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