23Na imaging: Worth its salt for understanding multiple sclerosis.
23Na imaging: Worth its salt for understanding multiple sclerosis.
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23Na 成像：对于了解多发性硬化症是值得的。
DOI：
10.1073/pnas.2110799118
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发表时间：
2021
影响因子：
11.1
通讯作者：
Hafler,DavidA
中科院分区：
文献类型：
--
作者：
Longbrake,ErinE;Hafler,DavidA
最近在体外和体内动物模型中的研究表明，钠是诱导自身免疫性疾病的许多环境因素之一，尽管缺乏患者的直接实验证据（1，2）。在PNAS中，Huhn et al. (3)发现多发性硬化症（MS）男性患者和实验性自身免疫性脑炎（EAE）小鼠皮肤钠沉积相对于健康对照组升高，通过钠MRI（23 Na-MRI）测量。通过定量证明组织盐储存的疾病特异性升高，他们建立了盐作为自身免疫的环境风险因素的生物学相关性，以及23 Na-MRI在体内研究这种现象的实用性。在过去的半个世纪中，自身免疫性疾病的发病率显著增加。虽然这类疾病的潜在遗传基础最近已被阐明，主要涉及免疫应答基因（4，5），但环境因素的变化最终必须推动这种增加（图1）。我们和其他人最近已经证明，较高的生理盐条件激活p38/MAPK通路，涉及NFAT 5和血清和糖皮质激素诱导的激酶1（SGK 1）在苦参碱诱导的Th 17极化（1，2）。基因沉默或化学抑制p38/MAPK，NFAT 5，或SGK 1废除高盐诱导的Th 17细胞的发展。在动物模型中，高盐饮食导致小鼠发生更严重的EAE（1，2）。还发现高盐与功能失调的FoxP 3调节性T细胞（Tcells）有关，诱导
Recent work both in vitro and in in vivo animal models has implicated sodium as one of a number of environmental factors in the induction of autoimmune disease, although direct experimental evidence in patients was lacking (1, 2). In PNAS, Huhn et al.(3) find that male patients with multiple sclerosis (MS) and mice with experimental autoimmune encephalitis (EAE) have elevated skin sodium deposition relative to healthy controls, as measured by sodium MRI (23Na-MRI). By quantitatively demonstrating disease-specific elevations in tissue salt stores, they establish the biological relevance of salt as an environmental risk factor for autoimmunity and the utility of 23Na-MRI for studying this phenomenon in vivo. There has been a marked increase in the incidence of autoimmune diseases in the last half-century. While the underlying genetic basis of this class of diseases has recently been elucidated implicating predominantly immune response genes (4, 5), changes in environmental factors must ultimately be driving this increase (Fig. 1). We and others have recently demonstrated that higher but physiologic salt conditions activate the p38/MAPK pathway involving NFAT5 and the serumand glucocorticoid-inducible kinase 1 (SGK1) during cytokine-induced Th17 polarization (1, 2). Gene silencing or chemical inhibition of p38/MAPK, NFAT5, or SGK1 abrogated the high-salt–induced Th17 cell development. In animal models, high-salt diets caused mice to develop more severe EAE (1, 2) It was also found that high salt was linked to dysfunctional FoxP3 regulatory T cells (Tregs), inducing