The vitamin D-dependent transcriptome of human monocytes

Area of Science:

• Immunology and Molecular Biology
• Nutritional Biochemistry

Background:

• Monocytes are crucial innate immune cells differentiating into macrophages and dendritic cells.
• The active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), acts via the vitamin D receptor (VDR).
• 1,25(OH)2D3 plays a key role in pathogen defense, including against tuberculosis, by modulating monocyte gene expression.

Purpose of the Study:

• To summarize insights from transcriptome-wide data of 1,25(OH)2D3-stimulated THP-1 human monocyte cells.
• To investigate the relationship between gene expression changes and epigenomic modifications induced by 1,25(OH)2D3.
• To identify key physiological functions and pathways affected by vitamin D in monocytes.

Main Methods:

• Utilized triplicate RNA sequencing (RNA-seq) to analyze the transcriptome of THP-1 cells after 1,25(OH)2D3 stimulation.
• Examined epigenomic changes, including chromatin accessibility and transcription factor binding (VDR, CTCF).
• Correlated transcriptomic data with genome-wide epigenomic data.

Main Results:

• Identified numerous primary and secondary vitamin D target genes that were up- and down-regulated.
• Observed 1,25(OH)2D3-dependent chromatin opening and altered genome-wide association of VDR and CTCF.
• The top early physiological function associated with vitamin D stimulation was the anti-microbial response, alongside activation of other immune pathways like IL10 signaling.

Conclusions:

• Epigenomic and transcriptomic responses in THP-1 cells provide a comprehensive model for vitamin D's impact on human physiology.
• Vitamin D actively modulates gene expression and epigenetic landscapes in monocytes, crucial for immune defense.
• The findings underscore vitamin D's significant role in regulating innate immunity and antimicrobial responses.