Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity
Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity
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DOI：
10.1016/j.jaut.2015.11.001
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发表时间：
2016-02-01
影响因子：
12.8
通讯作者：
Klotz, Luisa
中科院分区：
文献类型：
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作者：
Hucke, Stephanie;Eschborn, Melanie;Klotz, Luisa
过去几十年来，工业化国家多发性硬化症 (MS) 发病率的增加可能与饮食习惯的改变有关。如今，盐含量增加是西方饮食的一个重要特征，膳食盐 (NaCl) 摄入量的增加会促进致病性 T 细胞反应，从而导致中枢神经系统 (CNS) 自身免疫。鉴于巨噬细胞反应对中枢神经系统疾病传播的重要性，我们讨论了盐消耗对中枢神经系统自身免疫中巨噬细胞反应的影响。我们观察到，接受高 NaCl 饮食的患有 EAE 的小鼠表现出中枢神经系统内巨噬细胞浸润和激活的强烈增强，并伴随着 EAE 效应阶段疾病的加重。巨噬细胞的NaCI处理引发了强烈的促炎表型，其特征在于促炎细胞因子的产生增强、免疫刺激分子的表达增加以及T细胞增殖的抗原非依赖性促进。这种 NaCl 诱导的促炎巨噬细胞表型伴随着 NF-kB 和 MAPK 信号通路激活的增加。与未经处理的巨噬细胞相比，转移到患有 EAE 疾病的动物中会导致疾病显着恶化，这一发现说明了 NaCl 条件巨噬细胞的致病相关性。重要的是，在人类单核细胞中，氯化钠也会促进促炎表型，从而增强人类 T 细胞增殖。总而言之，高盐摄入量会促进促炎巨噬细胞的产生，从而加剧中枢神经系统自身免疫。与其他研究一起，这些结果强调需要进一步确定增加膳食盐摄入量与多发性硬化症严重程度的相关性。 (C) 2015 Elsevier Ltd. 保留所有权利。
The increasing incidence in Multiple Sclerosis (MS) during the last decades in industrialized countries might be linked to a change in dietary habits. Nowadays, enhanced salt content is an important characteristic of Western diet and increased dietary salt (NaCl) intake promotes pathogenic T cell responses contributing to central nervous system (CNS) autoimmunity. Given the importance of macrophage responses for CNS disease propagation, we addressed the influence of salt consumption on macrophage responses in CNS autoimmunity. We observed that EAE-diseased mice receiving a NaCl-high diet showed strongly enhanced macrophage infiltration and activation within the CNS accompanied by disease aggravation during the effector phase of EAE. NaCI treatment of macrophages elicited a strong pro inflammatory phenotype characterized by enhanced pro-inflammatory cytokine production, increased expression of immune-stimulatory molecules, and an antigen-independent boost of T cell proliferation. This NaCl-induced pro-inflammatory macrophage phenotype was accompanied by increased activation of NF-kB and MAPK signaling pathways. The pathogenic relevance of NaCl-conditioned macrophages is illustrated by the finding that transfer into EAE-diseased animals resulted in significant disease aggravation compared to untreated macrophages. Importantly, also in human monocytes, NaCl promoted a pro-inflammatory phenotype that enhanced human T cell proliferation. Taken together, high dietary salt intake promotes pro-inflammatory macrophages that aggravate CNS autoimmunity. Together with other studies, these results underline the need to further determine the relevance of increased dietary salt intake for MS disease severity. (C) 2015 Elsevier Ltd. All rights reserved.