Impact of vitamin D on immune function: lessons learned from genome-wide analysis

Abstract

Immunomodulatory responses to the active form of vitamin D (1,25-dihydroxyvitamin D, 1,25D) have been recognized for many years, but it is only in the last 5 years that the potential role of this in normal human immune function has been recognized. Genome-wide analyses have played a pivotal role in redefining our perspective on vitamin D and immunity. The description of increased vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1) expression in macrophages following a pathogen challenge, has underlined the importance of intracrine vitamin D as key mediator of innate immune function. It is now clear that both macrophages and dendritic cells (DCs) are able to respond to 25-hydroxyvitamin D (25D), the major circulating vitamin D metabolite, thereby providing a link between the function of these cells and the variations in vitamin D status common to many humans. The identification of hundreds of primary 1,25D target genes in immune cells has also provided new insight into the role of vitamin D in the adaptive immune system, such as the modulation of antigen-presentation and T cells proliferation and phenotype, with the over-arching effects being to suppress inflammation and promote immune tolerance. In macrophages 1,25D promotes antimicrobial responses through the induction of antibacterial proteins, and stimulation of autophagy and autophagosome activity. In this way variations in 25D levels have the potential to influence both innate and adaptive immune responses. More recent genome-wide analyses have highlighted how cytokine signaling pathways can influence the intracrine vitamin D system and either enhance or abrogate responses to 25D. The current review will discuss the impact of intracrine vitamin D metabolism on both innate and adaptive immunity, whilst introducing the concept of disease-specific corruption of vitamin D metabolism and how this may alter the requirements for vitamin D in maintaining a healthy immune system in humans.

Vitamin D Deficiency Does Not Result in a Breach of Host Defense in Murine Models of Pneumonia

“…Statistical analysis was performed by ANOVA and t test between control and malnutrition groups with no significant differences. host defense (39). VitD also acts together with several other regulatory mediators or hormones, which also modulate immunity (40).…”

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

“…First, most immune cells, both the innate and adaptive immune system, expresses the vitamin D receptor (VDR) [26][27][28]. Moreover, such immune cells exhibit an active vitamin D metabolism, with the expression of the rate-limiting enzyme for vitamin D synthesis, 1α-hydroxylase (CYP27B1) [29]. Immune cells are, therefore, able to synthesize and secrete Vitamin D in both an autocrine and paracrine way [29][30].…”

“…Moreover, such immune cells exhibit an active vitamin D metabolism, with the expression of the rate-limiting enzyme for vitamin D synthesis, 1α-hydroxylase (CYP27B1) [29]. Immune cells are, therefore, able to synthesize and secrete Vitamin D in both an autocrine and paracrine way [29][30]. Immune cell types targeted by vitamin D include 5 monocytes and macrophages, dendritic cells (DCs), T and B cells [31].…”

“…One study investigated cognitive effects of IU/day may be started when the deficiency has been corrected, and at once in case of vitamin D insufficiency (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) ng/mL). Since current evidence also suggests both obstetric and pediatric benefit from vitamin D against the risk of developing MS, vitamin D supplementation in children and pregnant women at risk of developing or being affected by MS should be considered [144].…”

Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation

“…[2][3][4] A vitamin D-enriched milieu maintains an immature DC phenotype associated with decreased ability to stimulate alloreactive T cells in MLCs. 5 Vitamin D deficiency has been associated with an increased incidence of chronic GvHD, 6 and supplementation with vitamin D to induce a tolerogenic DC population has been suggested for prevention of GvHD.…”