The vitamin D-dependent transcriptome of human monocytes

Abstract

Monocytes are important cells of the innate immune system that can differentiate into macrophages and dendritic cells. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), serves as a ligand of the nuclear receptor vitamin D receptor (VDR). A key physiological function of 1,25(OH)₂D₃ 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)₂D₃-affected genome-wide data are available. Here we summarize the insight obtained from the recent transcriptome of 1,25(OH)₂D₃-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)₂D₃-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)₂D₃-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)₂D₃ represent a master example of the impact of vitamin D on human physiology.

Keywords: Epigenome; Monocytes; RNA-seq; Transcriptome; VDR; Vitamin D.