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MAP7 and MUCL1 Are Biomarkers of Vitamin D3-Induced Tolerogenic Dendritic Cells in Multiple Sclerosis Patients

机译:MAP7和MUCL1是多发性硬化症患者中维生素D3诱导的致耐受树突状细胞的生物标志物

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摘要

The administration of autologous tolerogenic dendritic cells (tolDC) has become a promising alternative for the treatment of autoimmune diseases, such as multiple sclerosis (MS). Specifically, the use of vitamin D3 for the generation of tolDC (vitD3-tolDC) constitutes one of the most widely studied approaches, as it has evidenced significant immune regulatory properties, both in vitro and in vivo. In this article, we generated human vitD3-tolDC from monocytes from healthy donors and MS patients, characterized in both cases by a semi-mature phenotype, secretion of IL-10 and inhibition of allogeneic lymphocyte proliferation. Additionally, we studied their transcriptomic profile and selected a number of differentially expressed genes compared to control mature and immature dendritic cells for their analysis. Among them, qPCR results validated CYP24A1, MAP7 and MUCL1 genes as biomarkers of vitD3-tolDC in both healthy donors and MS patients. Furthermore, we constructed a network of protein interactions based on the literature, which manifested that MAP7 and MUCL1 genes are both closely connected between them and involved in immune-related functions. In conclusion, this study evidences that MAP7 and MUCL1 constitute robust and potentially functional biomarkers of the generation of vitD3-tolDC, opening the window for their use as quality controls in clinical trials for MS.
机译:自体耐受性树突状细胞(tolDC)的给药已成为治疗自身免疫性疾病(如多发性硬化症(MS))的有希望的替代方法。具体而言,使用维生素D3生成tolDC(vitD3-tolDC)构成了研究最广泛的方法之一,因为它已证明在体外和体内均具有显着的免疫调节特性。在本文中,我们从健康供体和MS患者的单核细胞中生成了人vitD3-tolDC,这两种情况均具有半成熟表型,IL-10的分泌和同种异体淋巴细胞增殖的抑制作用。此外,我们研究了它们的转录组谱,并选择了与对照成熟和未成熟树突状细胞相比的许多差异表达基因进行分析。其中,qPCR结果验证了CYP24A1,MAP7和MUCL1基因是vitD3-tolDC的生物标志物,在健康供体和MS患者中均如此。此外,我们根据文献构建了蛋白质相互作用的网络,这表明MAP7和MUCL1基因两者之间紧密相连,并参与免疫相关功能。总而言之,这项研究证明MAP7和MUCL1构成了vitD3-tolDC生成的强大且具有潜在功能的生物标志物,为在MS临床试验中用作质量控制打开了窗口。

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