Key Vitamin D Target Genes with Functions in the Immune System.
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.
['Koivisto|Oona|O|0000-0001-9355-0201', 'Hanel|Andrea|A|0000-0001-6022-4362', 'Carlberg|Carsten|C|0000-0003-2633-0684']
D030301:Activin Receptors, Type II D056704:Adaptive Immunity D023181:Antimicrobial Cationic Peptides D015551:Autoimmunity D022782:CCAAT-Enhancer-Binding Protein-beta D066264:Datasets as Topic D005353:Fibronectins D005786:Gene Expression Regulation D006801:Humans D007113:Immunity, Innate D007963:Leukocytes, Mononuclear D018950:Lipopolysaccharide Receptors D008562:Membrane Glycoproteins D018167:Receptors, Calcitriol D011951:Receptors, Complement D000074084:THP-1 Cells D059467:Transcriptome D014807:Vitamin D
Vitamin D vitamin D target genes immune system gene regulation VDR monocytes PBMCs epigenome transcriptome