Supplemental Digital Content is available in the text. 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.

中文翻译：

---

T 细胞中的表观遗传修饰

补充数字内容在文本中可用。SS（达尔盐敏感）大鼠是一种既定的高血压和肾损伤模型，伴随着对高盐饮食的免疫系统激活。对饮食中钠非依赖性和依赖性成分影响的研究表明，SS/MCW (JrHsdMcwi) 大鼠维持在纯化饮食 (AIN-76A) 上，表现出比谷物喂养更严重的表型SS/CRL (JrHsdMcwiCrl) 大鼠。由于免疫系统、环境和饮食的贡献被证明可以改变这种表型，因此本研究检查了从这些集落的外周和肾脏中分离的 T 细胞的表观遗传谱。从 2 个集落的肾脏分离的 T 细胞显示转录组和功能差异可能导致高血压和肾损伤的易感性。为响应高盐挑战，与 SS/CRL 肾脏 T 细胞相比，从 SS/MCW 肾脏分离的 T 细胞的甲基化组表现出差异甲基化区域的显着增加，并且偏好高甲基化。循环 T 细胞在集落之间表现出相似的甲基化特征。利用从进行 DNA 甲基化分析的同一动物身上分离的 T 细胞的转录组学数据，在所有组中观察到基因表达和 DNA 甲基化之间的主要负相关。最后，DNA甲基转移酶的抑制减弱了SS / MCW大鼠中盐诱导的高血压和肾损伤，为甲基化提供了功能作用。这项研究证明了表观遗传修饰对免疫细胞功能的影响，突出了进一步研究的必要性。