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以及多发性硬化症患者中维生素 D3 诱导的耐受性树突状细胞的生物标志物。

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

机构信息

Division of Immunology, LCMN, Germans Trias i Pujol University Hospital and Research Institute, Barcelona, Spain.

Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.

出版信息

Front Immunol. 2019 Jun 19;10:1251. doi: 10.3389/fimmu.2019.01251. eCollection 2019.

Abstract

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 and . 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 and 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 and genes are both closely connected between them and involved in immune-related functions. In conclusion, this study evidences that and 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.

摘要

自体耐受原性树突状细胞(tolDC)的给药已成为治疗自身免疫性疾病(如多发性硬化症(MS))的一种有前途的替代方法。具体来说,使用维生素 D3 来产生 tolDC(vitD3-tolDC)是研究最广泛的方法之一,因为它具有显著的免疫调节特性,既可以 ,也可以 。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,在这两种情况下,它们都表现出半成熟表型、IL-10 的分泌和抑制同种异体淋巴细胞增殖。此外,我们研究了它们的转录组谱,并选择了一些与对照成熟和不成熟树突状细胞相比差异表达的基因进行分析。其中,qPCR 结果验证了健康供体和 MS 患者中 vitD3-tolDC 的 和 基因作为生物标志物。此外,我们基于文献构建了一个蛋白质相互作用网络,该网络表明 和 基因之间彼此紧密相连,并且参与免疫相关功能。总之,本研究证明 和 是生成 vitD3-tolDC 的稳健且潜在功能的生物标志物,为其在 MS 的临床试验中用作质量控制提供了可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b5b/6598738/21039ac53576/fimmu-10-01251-g0001.jpg

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