Key Vitamin D Target Genes with Functions in the Immune System

Abstract

The biologically active form of vitamin D 3 , 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), 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) 2 D 3 , filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin D 3 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.

Detectable respiratory SARS-CoV-2 RNA is associated with low vitamin D levels and high social deprivation

“…Our data adds to results from other studies suggesting a possible role for vitamin D in COVID-19 infection [15]. As described previously there is mechanistic plausibility in view of vitamin D modulating immune function and viral replication [2,3]. A further positive aspect of our study is the inclusion of SARS-CoV-2 test negative patients which were suspected of a COVID-19 diagnosis for comparison (control group).…”

“…Introduction Research over the past 30 years has shown that in addition to the well-established functions as a mediator of calcium and bone metabolism, the hormone 1,25 dihydroxyvitamin D has effects on a range of pathological processes [1]. These include associations with pathogenesis of neoplastic, inflammatory, demyelinating, and cardiovascular diseases, as well as diabetes; the aetiology possibly being due to modulation of innate and adaptive immune functions via genes regulated by the transcription factor vitamin D receptor [2,3]. Hypovitaminosis D, identified by low serum levels of biologically inactive 25-hydroxyvitamin D (25-OHD), has a high worldwide prevalence [4].…”

An Update on Vitamin D Metabolism

“…We have already outlined that 1 α-hydroxylation produces the active hormone within different cells of immune system, where it exerts autocrine and paracrine effects. A very recent study on vitamin D target genes evaluated and compared all the available transcriptome-wide datasets from human monocytes treated with 1,25(OH) 2 D in vitro [94]. 15 VDR target genes with a potential pivotal role in the immune response were identified and classified in three groups.…”

“…Group 2 includes LILRB4, LRRC25, MAPK13, SEMA6B, THBD, and THEMIS2 genes, which are required in the general response to infection. Group 3 includes ACVRL1, CD93, CEBPB, NINJ1, SRGN, genes involved in long-term autoimmunity mechanisms, which do not require ligand binding to VDR and are likely involved in epigenomic regulation [94].…”

Vitamin D Update

“…A thorough review of vitamin D's regulatory function in both innate and acquired immunity can be found in Wei and Christakos [15]. The biologically active form of vitamin D, 1,25(OH)2D, modulates innate and adaptive immunity via regulation of at least 15 genes by the VDR [16]. 1,25(OH)2D upregulates CAMP not only in monocytes/ macrophages but also in other cells participating in the innate immune system.…”