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T helper cell polarity determines salt sensitivity and hypertension development

Hypertension Research volume 46, pages 2168–2178 (2023)Cite this article

Abstract

High-salt intake is known to induce pathogenic T helper (Th) 17 cells and hypertension, but contrary to what is known, causes hypertension only in salt-sensitive (SS) individuals. Thus, we hypothesized that Th cell polarity determines salt sensitivity and hypertension development. Cultured splenic T cells from Dahl SS and salt-resistant (SR) rats subjected to hypertonic salt solutions were evaluated via ELISA, flow cytometry, immunocytochemistry and RT-qPCR. Seven-week-old SS and SR rats were fed a chow (CD) or high-salt diet (HSD) for 4 weeks, with weekly measurements of systolic blood pressure. The relaxation response of the aorta rings to the cumulative addition of acetylcholine was measured ex vivo. In these experimental animals, the Th cell polarity (Th17 and T regulatory [Treg]), the expression of Th17- or Treg-related genes, and the enrichment of the transcription factors RORγt and FOXP3 on the target gene promoter regions were determined via flow cytometry, RT-qPCR, and chromatin immunoprecipitation. Hypertonic salt solution induced Th17 and Treg cell differentiation in cultured splenic T cells isolated from SS and SR rats, respectively. HSD induced hypertension, endothelial dysfunction and proinflammatory Th17 cell differentiation only in SS rats. The enrichment of RORγt on the promoter regions of Il17a and Il23r increased their expression only in SS rats. Regardless of HSD, SR rats remained normotensive with Treg polarity, causing high Treg-related gene expressions (Il10, Cd25 and Foxp3). This study demonstrated that Th cell polarity determines salt sensitivity and drives hypertension development. SR rats were protected from HSD-associated hypertension via anti-inflammatory Treg polarity.

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (NRF-2021R1A2B502001763, and 2021R1A4A1021617), and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C0001).

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Authors and Affiliations

  1. Department of Pharmacology, Kyungpook National University, Daegu, 41944, Republic of Korea

    Jee Young Kim, Soyung Lee, Sungmin Jang, Cheong-Wun Kim & Inkyeom Kim

  2. Cardiovascular Research Institute, Kyungpook National University, Daegu, 41944, Republic of Korea

    Jee Young Kim, Soyung Lee, Sungmin Jang, Cheong-Wun Kim & Inkyeom Kim

  3. BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, 41944, Republic of Korea

    Jee Young Kim, Soyung Lee, Sungmin Jang, Cheong-Wun Kim & Inkyeom Kim

  4. Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea

    Jee Young Kim, Soyung Lee, Sungmin Jang, Cheong-Wun Kim & Inkyeom Kim

  5. Department of Animal Science, College of Natural Resources & Live Science, Pusan National University, Miryang, 50463, Republic of Korea

    Bon-Hee Gu & Myunghoo Kim

  6. Life and Industry Convergence Research Institute, Pusan National University, Miryang, 50463, Republic of Korea

    Bon-Hee Gu & Myunghoo Kim

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Kim, J.Y., Lee, S., Jang, S. et al. T helper cell polarity determines salt sensitivity and hypertension development. Hypertens Res 46, 2168–2178 (2023). https://doi.org/10.1038/s41440-023-01365-0

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