The vitamin D-dependent transcriptome of human monocytes

Monocytes are important cells of the innate immune system that can differentiate into macrophages and dendritic cells. The biologically active form of vitamin D, 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3), serves as a ligand of the nuclear receptor vitamin D receptor (VDR). A key physiological function of 1,25(OH)(2)D-3 is the defense against pathogens, such as those causing tuberculosis, that involves the modulation of the monocyte transcriptome. THP-1 cells are an established model of human monocytes, for which the at present largest set of 1,25(OH)(2)D-3-affected genome-wide data are available. Here we summarize the insight obtained from the recent transcriptome of 1,25(OH)(2)D-3-stimulated THP-1 cells, that was determined by triplicate RNA sequencing (RNA-seq). Primary and secondary vitamin D target genes being up- and down-regulated were related to changes in the epigenome of THP-1 cells, such as 1,25(OH)(2)D-3-dependent chromatin opening and modulation of the genome-wide association of the transcription factors VDR and CCCTC-binding factor (CTCF) with their respective genomic binding sites. The anti-microbial response is the top-ranking early physiological function represented by 1,25(OH)(2)D-3-stimulated genomic regions and genes, but also other immunity-related pathways, such as IL10 signaling, are activated. Taken together, the epigenomic and transcriptomic responses of THP-1 cells to 1,25(OH)(2)D-3 represent a master example of the impact of vitamin D on human physiology. (C) 2015 Elsevier Ltd. All rights reserved.