Sex-specific T-cell regulation of angiotensin II-dependent hypertension.
Sex-specific T-cell regulation of angiotensin II-dependent hypertension.
复制标题
血管紧张素II依赖性高血压的性别特异性T细胞调节。
DOI：
10.1161/hypertensionaha.114.03663
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Sandberg K
中科院分区：
文献类型：
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作者：
Ji H;Zheng W;Li X;Liu J;Wu X;Zhang MA;Umans JG;Hay M;Speth RC;Dunn SE;Sandberg K
研究表明T细胞调节动脉压。由于免疫系统和高血压存在明显的性别差异，我们研究了雄性（M）和雌性（F）野生型（WT）和重组激活基因-1缺陷型（Rag 1 −/−）小鼠中血管紧张素II（Ang II）诱导的平均动脉压（MAP）升高的T细胞调节的性别差异。在Rag 1 −/−小鼠中，WT组MAP峰值的性别差异消失[mmHg：WT-F，136±4.9 vs. WT-M，153±1.7; P<0.02; Rag 1 −/−-F，135±2.1 vs. Rag 1 −/−-M，141±3.8]。过继转移雄性（CD 3 M → Rag 1 −/−-M）T细胞后的MAP峰值比过继转移雌性（CD 3F → Rag 1 −/−-M）T细胞后的MAP峰值高13 mmHg。CD 3 M → Rag 1 −/−-M小鼠的脾脏中产生促炎性白细胞介素-17 A（2.4倍）和肿瘤坏死因子-α（2.2倍）的T细胞频率较高，白细胞介素-10的血浆水平（13倍）和肾脏mRNA表达（2.4倍）较低，而CD 3F → Rag 1 −/−-M小鼠总体上显示出较高的激活状态和辅助T细胞1偏向性肾脏炎症。如果T细胞供体是男性而不是女性，则血管周围脂肪组织和肾脏中的T细胞浸润更大，并与对Ang II的升压反应增加相关，并且T细胞亚群扩增和组织浸润的这些性别差异在男性宿主中维持7-8周。因此，适应性免疫反应和促炎和抗炎细胞因子信号传导在高血压中的作用在性别之间是不同的，需要理解以改善男性和女性高血压相关疾病的治疗。
Studies suggest T cells modulate arterial pressure. Since robust sex differences exist in the immune system and in hypertension, we investigated sex differences in T cell modulation of angiotensin II (Ang II)-induced increases in mean arterial pressure (MAP) in male (M) and female (F) wild type (WT) and recombination-activating-gene-1-deficient (Rag1−/−) mice. Sex-differences in peak MAP in WT were lost in Rag1−/− mice [mmHg: WT-F, 136±4.9 vs. WT-M, 153±1.7; P<0.02; Rag1−/−-F, 135±2.1 vs. Rag1−/−-M, 141±3.8]. Peak MAP was 13 mmHg higher after adoptive transfer of male (CD3M→Rag1−/−-M) vs. female (CD3F→Rag1−/−-M) T-cells. CD3M→Rag1−/−-M mice exhibited higher splenic frequencies of pro-inflammatory interleukin-17A (2.4-fold) and tumor-necrosis factor-α (2.2-fold)-producing T cells and lower plasma levels (13-fold) and renal mRNA expression (2.4-fold) of interleukin-10 while CD3F→Rag1−/−-M mice displayed a higher activation state in general and T-helper 1-biased renal inflammation. Greater T cell infiltration into perivascular adipose tissue and kidney associated with increased pressor responses to Ang II if the T cell donor was male but not female and these sex differences in T cell subset expansion and tissue infiltration were maintained for 7–8 weeks within the male host. Thus, the adaptive immune response and role of pro- and anti-inflammatory cytokine signaling in hypertension is distinct between the sexes and needs to be understood to improve therapeutics for hypertension-associated disease in both men and women.