Magnesium increases numbers of Foxp3+ Treg cells and reduces arthritis severity and joint damage in an IL-10-dependent manner mediated by the intestinal microbiome.
Magnesium increases numbers of Foxp3+ Treg cells and reduces arthritis severity and joint damage in an IL-10-dependent manner mediated by the intestinal microbiome.
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DOI：
10.1016/j.ebiom.2023.104603
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发表时间：
2023-06
期刊：
影响因子：
11.1
通讯作者：
Gulko, Percio S.
中科院分区：
文献类型：
--
作者：
Laragione, Teresina;Harris, Carolyn;Azizgolshani, Nasim;Beeton, Christine;Bongers, Gerold;Gulko, Percio S.
类风湿性关节炎（RA）是一种常见的自身免疫性疾病，具有新兴的环境和微生物危险因素。西方饮食通常缺乏镁（Mg），有证据表明镁可能具有抗炎特性。但镁补充剂在关节炎或T细胞亚群中的实际作用尚未被探索。我们研究了高镁饮食在两种不同的KRN血清诱导的RA和胶原诱导的关节炎小鼠模型中的作用。我们还描述了脾细胞的表型、基因表达和广泛的肠道微生物组分析，包括粪便材料移植（FMT）。高Mg饮食组小鼠关节炎严重程度降低，关节损伤减轻，IL-1β、IL-6和TNFα表达降低。高Mg组Foxp3+ Treg细胞和产生il -10的T细胞数量增加。高Mg对IL-10基因敲除小鼠的保护作用消失。高镁饮食小鼠的FMT重现了饮食治疗小鼠的表型，关节炎严重程度降低，Foxp3+ Treg增加，产生il -10的T细胞增加。使用16S rDNA测序的肠道微生物组分析揭示了饮食特异性变化，包括高镁组中ra相关的普雷沃氏菌水平降低，而拟杆菌和其他与短链脂肪酸产量增加相关的细菌水平增加。宏基因组分析暗示了其他途径，包括l -色氨酸生物合成和精氨酸脱亚胺酶。我们描述了Mg在抑制关节炎、扩大Foxp3+ T细胞和IL-10产生中的新作用，并表明这些作用是由肠道微生物群介导的。我们的发现提示了一种新的策略来修改肠道微生物组来治疗类风湿性关节炎和其他自身免疫性和炎症性疾病。没有。
Rheumatoid arthritis (RA) is a common autoimmune disease with emerging environmental and microbiome risk factors. The western diet is typically deficient in magnesium (Mg), and there is some evidence suggesting that Mg may have anti-inflammatory properties. But the actual role of Mg supplementation in arthritis or in T cell subsets has not been explored. We investigated the role of a high Mg diet in two different mouse models of RA induced with the KRN serum, and collagen-induced arthritis. We also characterized the phenotypes of splenocytes, gene expression, and an extensive intestinal microbiome analyses including fecal material transplantation (FMT). The high Mg diet group was significantly protected with reduced arthritis severity and joint damage, and reduced expression of IL-1β, IL-6, and TNFα. The high Mg group also had increased numbers of Foxp3+ Treg cells and IL-10-producing T cells. The high Mg protective effect disappeared in IL-10 knockout mice. FMT from the high Mg diet mice recreated the phenotypes seen in the diet-treated mice, with reduced arthritis severity, increased Foxp3+ Treg, and increased IL-10-producing T cells. Intestinal microbiome analyses using 16S rDNA sequencing revealed diet-specific changes, including reduced levels of RA-associated Prevotella in the high Mg group, while increasing levels of Bacteroides and other bacteria associated with increased production of short-chain fatty acids. Metagenomic analyses implicated additional pathways including L-tryptophan biosynthesis and arginine deiminase. We describe a new role for Mg in suppressing arthritis, in expanding Foxp3+ T reg cells and in the production of IL-10, and show that these effects are mediated by the intestinal microbiome. Our discoveries suggest a novel strategy for modifying the intestinal microbiome to treat RA and other autoimmune and inflammatory diseases. None.
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