Vaartjes Daniëlle, Nandakumar Kutty-Selva, Holmdahl Rikard, Raposo Bruno
Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Section for Medical Inflammation Research, Southern Medical University, Guangzhou, China.
Immunology. 2018 Mar 7;154(4):683-94. doi: 10.1111/imm.12923.
High salt consumption has since long been associated with elevated blood pressure and cardiovascular disease. Recently, mouse studies suggested that a high dietary salt intake exacerbates the clinical manifestations of autoimmunity. Using naïve cells ex vivo after pre-exposure of mice to high salt intake, we showed that increased salt exposure affects the viability and effector functions of immune cells. CD4 T-cells evidenced a pro-inflammatory phenotype characterized by increased secretion of IFNγ and IL-17A, when exposed to high salt concentrations in vitro. Interestingly, this phenotype was associated with osmotic pressure, as replacing salt for d-mannitol resulted in similar observations. However, high salt intake did not alter the development of T-cell-dependent autoimmunity. Instead, recruitment of peritoneal macrophages was increased in mice pre-exposed to high salt concentrations. These cells had an increased production of both TNFα and IL-10, suggesting that salt stimulates expansion and differentiation of different subsets of macrophages. Moreover, mice pre-exposed to high salt intake developed exacerbated symptoms of colitis, when induced by dextran sulphate sodium. The aggravated colitis in salt-exposed animals was associated with a higher frequency of CD4 T-cells and CD11b CD64 macrophages producing TNFα. These phenotypes correlated with elevated titres of faecal IgA and higher lymphocytic cellularity in the colon, mesenteric lymph nodes and spleen. In conclusion, we report here that high salt intake affects both lymphoid and myeloid cells ex vivo. However, the effects of high salt intake in vivo seem less pronounced in terms of CD4 T-cell responses, whereas macrophage-dependent pathologies are significantly influenced.
长期以来，高盐摄入一直与血压升高和心血管疾病有关。最近，小鼠研究表明，高盐饮食摄入会加剧自身免疫的临床表现。在将小鼠预先暴露于高盐摄入后，使用离体的未致敏细胞，我们发现增加盐暴露会影响免疫细胞的活力和效应功能。当在体外暴露于高盐浓度时，CD4 T细胞表现出促炎表型，其特征是IFNγ和IL-17A分泌增加。有趣的是，这种表型与渗透压有关，因为用d-甘露醇替代盐会得到类似的结果。然而，高盐摄入并未改变T细胞依赖性自身免疫的发展。相反，在预先暴露于高盐浓度的小鼠中，腹膜巨噬细胞的募集增加。这些细胞中TNFα和IL-10的产生均增加，表明盐刺激了不同巨噬细胞亚群的扩增和分化。此外，预先暴露于高盐摄入的小鼠在右旋糖酐硫酸钠诱导下会出现加重的结肠炎症状。盐暴露动物中加重的结肠炎与产生TNFα的CD4 T细胞和CD11b CD64巨噬细胞的较高频率有关。这些表型与粪便IgA滴度升高以及结肠、肠系膜淋巴结和脾脏中淋巴细胞细胞增多有关。总之，我们在此报告，高盐摄入在体外会影响淋巴细胞和髓细胞。然而，就CD4 T细胞反应而言，高盐摄入在体内的影响似乎不太明显，而巨噬细胞依赖性病理则受到显著影响。
