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人类外周血初级免疫细胞中微量营养素维生素 D 的常见和个体靶基因。

Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood.

机构信息

School of Medicine, Institute of Biomedicine, University of Eastern Finland, POB 1627, 70211, Kuopio, Finland.

Institute for Applied Mathematics, Merida Research Unit, National Autonomous University of Mexico, Sierra Papacal, Merida, Yucatan, Mexico.

出版信息

Sci Rep. 2020 Dec 3;10(1):21051. doi: 10.1038/s41598-020-78288-0.

Abstract

Vitamin D is essential for the function of the immune system. In this study, we treated peripheral blood mononuclear cells (PBMCs) of healthy adults with the biologically active form of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)D) using two different approaches: single repeats with PBMCs obtained from a cohort of 12 individuals and personalized analysis based on triplicates of five study participants. This identified 877 (cohort approach) and 3951 (personalized approach) genes that significantly (p < 0.05) changed their expression 24 h after 1,25(OH)D stimulation. From these, 333 and 1232 were classified as supertargets, a third of which were identified as novel. Individuals differed largely in their vitamin D response not only by the magnitude of expression change but also by their personal selection of (super)target genes. Functional analysis of the target genes suggested the overarching role of vitamin D in the regulation of metabolism, proliferation and differentiation, but in particular in the control of functions mediated by the innate and adaptive immune system, such as responses to infectious diseases and chronic inflammatory disorders. In conclusion, immune cells are an important target of vitamin D and common genes may serve as biomarkers for personal responses to the micronutrient.

摘要

维生素 D 对于免疫系统的功能至关重要。在这项研究中,我们使用两种不同的方法用生物活性形式的维生素 D,1α,25-二羟维生素 D(1,25(OH)D)处理健康成年人的外周血单核细胞(PBMCs):用来自 12 个人群的 PBMCs 进行单次重复处理,以及基于五名研究参与者的三份重复进行个性化分析。这确定了 877 个(队列方法)和 3951 个(个性化方法)基因,它们在 1,25(OH)D 刺激后 24 小时显著(p < 0.05)改变了它们的表达。其中,333 个和 1232 个被归类为超级靶标,其中三分之一被鉴定为新的。个体之间的维生素 D 反应差异很大,不仅表现在表达变化的幅度上,还表现在他们对(超级)靶基因的个人选择上。靶基因的功能分析表明,维生素 D 在调节代谢、增殖和分化方面起着主导作用,但特别是在控制先天和适应性免疫系统介导的功能方面,例如对传染病和慢性炎症性疾病的反应。总之,免疫细胞是维生素 D 的重要靶标,常见基因可能作为个体对微量营养素反应的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f702/7713372/d3fb497d6b26/41598_2020_78288_Fig1_HTML.jpg

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