ABSTRACT
Immune cells, including dendritic cells, macrophages, and T and B cells, express the vitamin D receptor and 1α-hydroxylase. In vitro studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, has an anti-inflammatory effect. Recent epidemiological evidence has indicated a significant association between vitamin D deficiency and an increased incidence, or aggravation, of infectious diseases and inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the impact of vitamin D on treatment and prevention, particularly in infectious diseases such as the 2019 coronavirus disease (COVID-19), remains controversial. Here, we review recent evidence associated with the relationship between vitamin D and inflammatory diseases and describe the underlying immunomodulatory effect of vitamin D.
Subject(s)
COVID-19 Drug Treatment , COVID-19/prevention & control , Immune System/drug effects , Inflammation/drug therapy , Vitamin D/therapeutic use , Animals , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/prevention & control , Autoimmune Diseases/drug therapy , B-Lymphocytes/immunology , Dendritic Cells/immunology , Disease Models, Animal , Humans , Influenza, Human/drug therapy , Influenza, Human/prevention & control , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/prevention & control , Macrophages/immunology , Mice , Monocytes/immunology , Multiple Sclerosis/drug therapy , Multiple Sclerosis/prevention & control , Receptors, Calcitriol/genetics , Receptors, Calcitriol/physiology , T-Lymphocytes/immunology , Vitamin D Deficiency/complicationsABSTRACT
The last couple of decades have seen an explosion in our interest and understanding of the role of vitamin D in the regulation of immunity. At the molecular level, the hormonal form of vitamin D signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. The VDR and vitamin D metabolic enzymes are expressed throughout the innate and adaptive arms of the immune system. The advent of genome-wide approaches to gene expression profiling have led to the identification of numerous VDR-regulated genes implicated in the regulation of innate and adaptive immunity. The molecular data infer that vitamin D signaling should boost innate immunity against pathogens of bacterial or viral origin. Vitamin D signaling also suppresses inflammatory immune responses that underlie autoimmunity and regulate allergic responses. These findings have been bolstered by clinical studies linking vitamin D deficiency to increased rates of infections, autoimmunity, and allergies. Our goals here are to provide an overview of the molecular basis for immune system regulation and to survey the clinical data from pediatric populations, using randomized placebo-controlled trials and meta-analyses where possible, linking vitamin D deficiency to increased rates of infections, autoimmune conditions, and allergies, and addressing the impact of supplementation on these conditions.
Subject(s)
Adaptive Immunity , Autoimmunity , Child Nutritional Physiological Phenomena/immunology , Dietary Supplements , Immunity, Innate , Immunologic Factors , Vitamin D/pharmacology , Vitamin D/physiology , Age Factors , Autoimmune Diseases/etiology , Child , Child, Preschool , Communicable Diseases/etiology , Female , Humans , Hypersensitivity/etiology , Infant , Male , Receptors, Calcitriol/metabolism , Receptors, Calcitriol/physiology , Signal Transduction/physiology , Vitamin D/metabolism , Vitamin D Deficiency/complications , Vitamin D Deficiency/immunologyABSTRACT
The biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), 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)2D3, filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin D3 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.