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Abstract：
Vitamin D modulates innate and adaptive immunity, the molecular mechanisms of which we aim to understand under human in vivo conditions. Therefore, we designed the study VitDHiD (NCT03537027) as a human investigation, in which 25 healthy individuals were supplemented with a single vitamin D3 bolus (80,000 IU). Transcriptome-wide differential gene expression analysis of peripheral blood mononuclear cells (PBMCs), which were isolated directly before and 24 h after supplementation, identified 452 genes significantly (FDR < 0.05) responding to vitamin D. In vitro studies using PBMCs from the same individuals confirmed 138 of these genes as targets of 1α,25-dihydroxyvitamin D3. A subset of the 91 most regulated in vivo vitamin D target genes indicated focal adhesion as the major pathway being upregulated by vitamin D3 supplementation of healthy individuals. Differences in the individual-specific responsiveness of in vivo vitamin D target genes in relation to the increase of the person\'s vitamin D status allowed a segregation of the VitDHiD participants into 9 high, 12 mid and 4 low responders. The expression profile of nearly 600 genes elucidate the difference between high and low vitamin D responders, the most prominent of which is the HLA-C (major histocompatibility complex, class I, C) gene.
摘要：
维生素D调节先天和适应性免疫，我们旨在理解在人类体内条件下的分子机制。因此,我们设计了这项研究VitDHiD（NCT03537027）作为人类调查，其中25名健康个体补充了单一的维生素D3推注（80,000IU）。外周血单个核细胞(PBMC)全转录组差异基因表达分析,在补充之前和之后24小时直接分离，鉴定出452个基因显着（FDR<0.05）响应维生素D。使用来自相同个体的PBMC进行的体外研究证实了138个这些基因作为1α的靶标，25-二羟基维生素D3。91个体内最受调节的维生素D靶基因的子集表明粘着斑是健康个体补充维生素D3上调的主要途径。体内维生素D靶基因的个体特异性反应性与人的维生素D状态增加的差异允许VitDHiD参与者分离为9高，12个中等和4个低响应者。近600个基因的表达谱阐明了高和低维生素D反应者之间的差异，其中最突出的是HLA-C(主要组织相容性复合体，I类,C)基因。
