Vitamin D and Immunity in Infants and Children

Abstract

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.

Keywords: allergies; autoimmunity; infectious diseases; innate immunity; pediatric populations; vitamin D deficiency.

Figure 1

Vitamin D signaling in innate immunity. Intracrine production 1,25D from CYP27B1-catalyzed conversion of circulating 25D in activated macrophages and dendritic cell is shown. The induction of expression by 1,25D signaling through the VDR of genes encoding several types of proteins implicated in innate immune signaling, including cytokines/chemokines, pattern recognition receptors (PRRs) and antimicrobial peptides (AMPs), is indicated. 1,25D signaling within and release from dendritic cells influences dendritic cell maturation and suppresses production of inflammatory Th1 and Th17 cells, favouring Th2 and Tregs. See text for details.