Vitamin-D in the Immune System: Genomic and Non-Genomic Actions

Abstract

More than thirty years ago functions of vitamin D other than its beneficial effects on calcium homeostasis and bone metabolism have been identified, mainly in relation to its antiproliferative effects on cancer cells. Notably, vitamin D deficiency has been associated with a number of pathological conditions, including infections, autoimmune and allergic diseases. Vitamin D, and its metabolites, are actively involved in the regulation of innate and adaptive immune responses. Vitamin D signals through the vitamin D receptor (VDR), a specific zinc-finger nuclear receptor. The functions of vitamin D are characterized as genomic, mediated through the VDR transcriptional effects inside the cell nucleus, and non-genomic, when the VDR induces rapid signaling, situated on the cell membrane and/or cytoplasm. Emerging evidence supports the notion that vitamin D enhances immunity, providing protection towards pathogens, while, concomitantly, it exerts immunosuppressive effects by preventing the detrimental effects of prolonged inflammatory responses to the host. Still, the precise molecular mechanisms involved in vitamin D's genomic and non-genomic actions remain incompletely defined. Moreover, it is unclear whether vitamin D actions require the synergistic activation of other mediators, such as nuclear membrane receptors. Understanding the biology of vitamin D and the molecular pathways utilized will pave the way for the design of more effective therapeutic strategies. In this review, we present the recent genomic and non-genomic effects of vitamin D from an immunological perspective with a focus on immune-mediated diseases.

Vitamin D and Physical Activity

“…Vitamin D affects the innate and adaptive immunity via VDRs [116][117][118]. Vitamin D enhances monocyte/macrophage activity.…”

Vitamin D and Multiple Sclerosis: An Update

“…It is a secosteroid and is primarily responsible for maintaining calcium homeostasis by facilitating absorption and utilization of minerals; as a result, it acts as a major contributor toward bone formation and homeostasis (15,(20)(21)(22)(23)(24). The naturally occurring form of vitamin D is biologically inactive and requires hydroxylation in the liver and kidney for activation (25).…”

“…It plays a key role in several other processes like cellular growth, proliferation, differentiation, and apoptosis; DNA repair and oxidative stress; and membrane transport and adhesion (15,(22)(23)(24). Recent studies have proposed that its supportive role in immune response reflects its involvement in the prevention of various diseases including brain disorders and cancer (15,33,36,37).…”

“…The binding of vitamin D (1, 25 (OH)2D3, calcitriol) to VDR and its subsequent activation leads to its heterodimerization with the retinoid-X receptor (RXR), resulting in modulation of vitamin D responsive gene expression by translocation of heterodimer complex (1, 25 (OH)2D3-VDR/RXR) to nucleus, and its recruitment on vitamin D response elements (VDRE) of target genes (24,40). The schematic pathway for vitamin D-based signaling is given in Figure 3.…”

Vitamina D e Melanoma

“…10 A não genómica resulta da ligação da vitamina D ativa aos VDRs, ativando assim as cascatas de sinalização celular. 11 Apesar do seu papel ser crucial na homeostasia do cálcio e fósforo, 12 a vitamina D é muito importante noutros mecanismos. Os VDRs estão presentes em cerca de 60 tipos de células 13 pelo que muitas das suas possíveis funções estão ainda por estudar.…”