# Patterns of transcriptional response to 1,25-dihydroxyvitamin D3 and bacterial lipopolysaccharide in primary human monocytes

## TL;DR

This study explores how vitamin D and bacterial signals affect gene activity in human monocytes, revealing immune pathways and ethnic differences in response.

## Contribution

The study identifies novel transcriptional patterns and ethnic differences in immune response to vitamin D and LPS in human monocytes.

## Key findings

- 1,25D up-regulates antimicrobial and autophagy genes while down-regulating pro-inflammatory genes in monocytes.
- Joint Bayesian analysis reveals shared transcriptional response patterns and enriched pathways like mTOR and IL-8 signaling.
- Inter-ethnic differences in transcriptional response to 1,25D and LPS suggest variability in immune modulation between ethnic groups.

## Abstract

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), plays an important immunomodulatory role, regulating transcription of genes in the innate and adaptive immune system. The present study examines patterns of transcriptome-wide response to 1,25D and the bacterial lipopolysaccharide (LPS) in primary human monocytes, to elucidate pathways underlying the effects of 1,25D on the immune system. Monocytes obtained from healthy individuals of African-African and European-American ancestry were treated with 1,25D alone or in the presence of LPS, which induced significant up-regulation of genes in the antimicrobial and autophagy pathways, while pro-inflammatory response genes were significantly down-regulated. A joint Bayesian analysis enabled clustering of genes into patterns of shared transcriptional response across treatments. The biological pathways enriched within these expression patterns highlighted several mechanisms through which 1,25D could exert its immunomodulatory role. Pathways such as mTOR signaling, EIF2 signaling, IL-8 signaling and Tec Kinase signaling were enriched among genes with opposite transcriptional responses to 1,25D and LPS, respectively, highlighting the important roles of these pathways in mediating the immunomodulatory activity of 1,25D. Furthermore, a subset of genes with evidence of inter-ethnic differences in transcriptional response was also identified, suggesting that in addition to the well-established inter-ethnic variation in circulating levels of vitamin D, the intensity of transcriptional response to 1,25D and LPS also varies between ethnic groups. We propose that dysregulation of the pathways identified in this study could contribute to immune-mediated disease risk.