Related Experiment Video
Updated: Jun 19, 2025
In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
Published on: January 22, 2020
In vivo vitamin D target genes interconnect key signaling pathways of innate immunity
Julia Jaroslawska1, Ranjini Ghosh Dastidar1, Carsten Carlberg1,2
1Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Abstract:
The vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), its nuclear receptor VDR (vitamin D receptor) and hundreds of their target genes are not only key regulators of calcium homeostasis, but also important modulators of the immune system. Innate immune cells like monocytes use VDR for efficient differentiation and are very responsive to vitamin D. So far, most information on the gene regulatory function of vitamin D and its physiological impact had been obtained from in vitro studies using supraphysiological doses of 1,25(OH)2D3. Therefore, medical experiments like the study VitDHiD (NCT03537027), where 25 healthy individuals were supplemented once with a vitamin D3 bolus (80,000 IU), provide important insight into the response to vitamin D under in vivo conditions. In this study, we inspected 452 in vivo vitamin D target genes from peripheral blood mononuclear cells (PBMCs) detected in VitDHiD and found 61 of them involved in eight major KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of innate immunity. Under in vivo conditions in healthy individuals vitamin D either silences five pathways of innate immunity, stabilizes two and increases one, so that acute inflammation is suppressed and the release of cytokines is kept under control. A ranking of the 61 target genes by inducibility, basal expression and multiple involvements in the pathways highlighted the genes NFKBIA (NFκB inhibitor alpha), NFKBIZ, FOSL2 (FOS like 2, AP1 transcription factor subunit), JDP2 (Jun dimerization protein 2), PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1), CLEC7A (C-type lectin domain containing 7A), DUSP6 (dual specificity phosphatase 6), NCF2 (neutrophil cytosolic factor 2), PLCB1 (phospholipase C beta 1), PLCG2 and TNFAIP3 (TNF alpha induced protein 3). In conclusion, vitamin D's in vivo effect on innate immunity in healthy adults is mediated by the interconnection of the pathways of neutrophil extracellular trap formation, Toll-like receptor, chemokine and phagosome signaling, NOD-like receptor, C-type lectin receptor, apoptosis and interleukin 17 through a limited set of proteins encoded by key target genes.
Insights
Vitamin D modulates innate immunity by regulating key genes in immune pathways. This study reveals how vitamin D affects inflammation and cytokine release in vivo, highlighting specific target genes for immune control.
Area of Science:
- Immunology
- Endocrinology
- Molecular Biology
Background:
- 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its receptor VDR regulate calcium homeostasis and the immune system.
- Innate immune cells like monocytes utilize VDR for differentiation and are responsive to vitamin D.
- Previous research primarily used in vitro studies with supraphysiological doses, limiting understanding of in vivo effects.
Purpose of the Study:
- To investigate the in vivo gene regulatory effects of vitamin D on innate immunity in healthy individuals.
- To identify vitamin D target genes and their involvement in major innate immunity pathways.
- To elucidate the mechanisms by which vitamin D influences immune responses under physiological conditions.
Main Methods:
- Analysis of 452 in vivo vitamin D target genes in peripheral blood mononuclear cells (PBMCs) from the VitDHiD study (NCT03537027).
- Individuals received a single 80,000 IU vitamin D3 bolus.
- Identification of genes within eight major KEGG pathways related to innate immunity and ranking based on inducibility, expression, and pathway involvement.
Main Results:
- 61 of the 452 identified vitamin D target genes were involved in eight major innate immunity pathways.
- In vivo, vitamin D suppressed five pathways, stabilized two, and upregulated one, collectively controlling acute inflammation and cytokine release.
- Key genes identified include NFKBIA, FOSL2, PIK3R1, CLEC7A, DUSP6, NCF2, PLCB1, PLCG2, and TNFAIP3.
Conclusions:
- Vitamin D's in vivo impact on innate immunity in healthy adults involves a network of specific immune pathways.
- These pathways include neutrophil extracellular trap formation, TLR, chemokine, phagosome, NLR, CLR, apoptosis, and IL-17 signaling.
- The immune modulation is mediated by a defined set of proteins encoded by key vitamin D target genes.
Related Concept Videos
01:23Role of Skin in Vitamin D Synthesis
The solar UV B rays (290-315 nm) are absorbed by the skin, and 7-dehydrocholesterol (provitamin D3) photolyzes it to previtamin D3, which undergoes a rapid transformation to vitamin...
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
01:20The JAK-STAT Signaling Pathway
01:16TGF - β Signaling Pathway
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...