Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
School of Applied Sciences, University of Brighton, Brighton, United Kingdom.
Front Immunol. 2022 Feb 24;13:790444. doi: 10.3389/fimmu.2022.790444. eCollection 2022.
Vitamin D is best known for its role in maintaining bone health and calcium homeostasis. However, it also exerts a broad range of extra-skeletal effects on cellular physiology and on the immune system. Vitamins D and D share a high degree of structural similarity. Functional equivalence in their vitamin D-dependent effects on human physiology is usually assumed but has in fact not been well defined experimentally. In this study we seek to redress the gap in knowledge by undertaking an in-depth examination of changes in the human blood transcriptome following supplementation with physiological doses of vitamin D and D. Our work extends a previously published randomized placebo-controlled trial that recruited healthy white European and South Asian women who were given 15 µg of vitamin D or D daily over 12 weeks in wintertime in the UK (Nov-Mar) by additionally determining changes in the blood transcriptome over the intervention period using microarrays. An integrated comparison of the results defines both the effect of vitamin D or D on gene expression, and any influence of ethnic background. An important aspect of this analysis was the focus on the changes in expression from baseline to the 12-week endpoint of treatment each individual, harnessing the longitudinal design of the study. Whilst overlap in the repertoire of differentially expressed genes was present in the D or D-dependent effects identified, most changes were specific to either one vitamin or the other. The data also pointed to the possibility of ethnic differences in the responses. Notably, following vitamin D supplementation, the majority of changes in gene expression reflected a down-regulation in the activity of genes, many encoding pathways of the innate and adaptive immune systems, potentially shifting the immune system to a more tolerogenic status. Surprisingly, gene expression associated with type I and type II interferon activity, critical to the innate response to bacterial and viral infections, differed following supplementation with either vitamin D or vitamin D, with only vitamin D having a stimulatory effect. This study suggests that further investigation of the respective physiological roles of vitamin D and vitamin D is warranted.
维生素 D 最为人知的是其在维持骨骼健康和钙平衡方面的作用。然而，它在细胞生理学和免疫系统方面也具有广泛的非骨骼作用。维生素 D 和 D 具有高度的结构相似性。通常假设它们在维生素 D 依赖性对人体生理学的影响方面具有功能等效性，但实际上并没有通过实验很好地定义。在这项研究中，我们通过深入研究补充生理剂量的维生素 D 和 D 后人体血液转录组的变化来弥补知识空白。我们的工作扩展了以前发表的一项随机安慰剂对照试验，该试验招募了健康的白种欧洲人和南亚妇女，在英国（11 月至 3 月）的冬季每天给予 15 µg 的维生素 D 或 D，持续 12 周，并通过微阵列在干预期间确定血液转录组的变化。对结果的综合比较定义了维生素 D 或 D 对基因表达的影响，以及种族背景的任何影响。该分析的一个重要方面是关注每个个体从基线到治疗 12 周终点的表达变化，利用研究的纵向设计。虽然 D 或 D 依赖性效应中存在差异表达基因的谱重叠，但大多数变化是特定于一种维生素或另一种维生素的。该数据还表明了种族差异在反应中的可能性。值得注意的是，在补充维生素 D 后，基因表达变化的大多数反映了基因活性的下调，许多基因编码先天和适应性免疫系统的途径，可能使免疫系统向更耐受的状态转变。令人惊讶的是，与 I 型和 II 型干扰素活性相关的基因表达在补充维生素 D 或 D 后有所不同，只有维生素 D 具有刺激作用。这项研究表明，需要进一步研究维生素 D 和 D 的各自生理作用。
