Epigenetic Modifications in T Cells: The Role of DNA Methylation in Salt-Sensitive Hypertension

John Henry Dasinger, Ammar J. Alsheikh, Justine M. Abais-Battad, Xiaoqing Pan, Daniel J. Fehrenbach, Hayley Lund, Michelle L. Roberts, Allen W. Cowley, Srividya Kidambi, Theodore A. Kotchen, Pengyuan Liu, Mingyu Liang, David L. Mattson

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The SS (Dahl salt sensitive) rat is an established model of hypertension and renal damage that is accompanied with immune system activation in response to a high-salt diet. Investigations into the effects of sodium-independent and dependent components of the diet were shown to affect the disease phenotype with SS/MCW (JrHsdMcwi) rats maintained on a purified diet (AIN-76A) presenting with a more severe phenotype relative to grain-fed SS/CRL (JrHsdMcwiCrl) rats. Since contributions of the immune system, environment, and diet are documented to alter this phenotype, this present study examined the epigenetic profile of T cells isolated from the periphery and the kidney from these colonies. T cells isolated from kidneys of the 2 colonies revealed that transcriptomic and functional differences may contribute to the susceptibility of hypertension and renal damage. In response to high-salt challenge, the methylome of T cells isolated from the kidney of SS/MCW exhibit a significant increase in differentially methylated regions with a preference for hypermethylation compared with the SS/CRL kidney T cells. Circulating T cells exhibited similar methylation profiles between colonies. Utilizing transcriptomic data from T cells isolated from the same animals upon which the DNA methylation analysis was performed, a predominant negative correlation was observed between gene expression and DNA methylation in all groups. Lastly, inhibition of DNA methyltransferases blunted salt-induced hypertension and renal damage in the SS/MCW rats providing a functional role for methylation. This study demonstrated the influence of epigenetic modifications to immune cell function, highlighting the need for further investigations.

Original languageEnglish (US)
Pages (from-to)372-382
Number of pages11
JournalHypertension
DOIs
StatePublished - Feb 1 2020

Keywords

  • T lymphocytes
  • diet
  • epigenomics
  • hypertension
  • methylation

ASJC Scopus subject areas

  • Internal Medicine

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    Dasinger, J. H., Alsheikh, A. J., Abais-Battad, J. M., Pan, X., Fehrenbach, D. J., Lund, H., Roberts, M. L., Cowley, A. W., Kidambi, S., Kotchen, T. A., Liu, P., Liang, M., & Mattson, D. L. (2020). Epigenetic Modifications in T Cells: The Role of DNA Methylation in Salt-Sensitive Hypertension. Hypertension, 372-382. https://doi.org/10.1161/HYPERTENSIONAHA.119.13716