%0 Clinical Study
%T In vivo vitamin D targets reveal the upregulation of focal adhesion-related genes in primary immune cells of healthy individuals.
%A Ghosh Dastidar R
%A Jaroslawska J
%A Malinen M
%A Tuomainen TP
%A Virtanen JK
%A Bendik I
%A Carlberg C
%J Sci Rep
%V 14
%N 1
%D 2024 07 30
%M 39080417
%F 4.996
%R 10.1038/s41598-024-68741-9
%X 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.