Abstract
The biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), modulates innate and adaptive immunity via genes regulated by the transcription factor vitamin D receptor (VDR). In order to identify the key vitamin D target genes involved in these processes, transcriptome-wide datasets were compared, which were obtained from a human monocytic cell line (THP-1) and peripheral blood mononuclear cells (PBMCs) treated in vitro by 1,25(OH)2D3, filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin D3 bolus. The led to the genes ACVRL1, CAMP, CD14, CD93, CEBPB, FN1, MAPK13, NINJ1, LILRB4, LRRC25, SEMA6B, SRGN, THBD, THEMIS2 and TREM1. Public epigenome- and transcriptome-wide data from THP-1 cells were used to characterize these genes based on the level of their VDR-driven enhancers as well as the level of the dynamics of their mRNA production. Both types of datasets allowed the categorization of the vitamin D target genes into three groups according to their role in (i) acute response to infection, (ii) infection in general and (iii) autoimmunity. In conclusion, 15 genes were identified as major mediators of the action of vitamin D in innate and adaptive immunity and their individual functions are explained based on different gene regulatory scenarios.
Highlights
Vitamin D3 is known as a micronutrient that is essential for calcium homeostasis and bone formation [1,2]
We aimed to provide a shortlist of vitamin D target genes that are of key importance in the immune system
In order to identify common vitamin D target genes in immune related cell types, we used the results of three different RNA-seq datasets
Summary
Vitamin D3 is known as a micronutrient that is essential for calcium homeostasis and bone formation [1,2]. A fully potent VDR protein evolved some 550 million years ago in a boneless vertebrate, i.e., at a time when there was no need for calcium homeostasis and bone formation [6,7,8]. VDR and its ligand first specialized in the modulation of innate and adaptive immunity, such as fighting against bacterial and viral infections [10,11] and preventing autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis [12,13], before they took on the additional task of regulating bone metabolism.
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