Vitamin D 3 is produced in the skin through the action of sun rays on a derivative of cholesterol, 7-dehydrocholesterol, to produce previtamin D 3. The biologic importance of such locally produced 1,25(OH) 2 D 3 emerged from its ability to promote cell differentiation in prostate cancer and colon cancer cells [7,8]. Fathallahpour A. Furthermore, 25(OH)D serum levels were reported to correlate with seasonality, while a supplementation with standard doses of oral cholecalciferol was found not effective in normalising serum 25(OH)D values [89, 90]. A recent Genome-Wide Association Study of almost 34,000 individuals showed that SNPs within the DBP gene are a key inherited determinant of low vitamin D status (serum 25D <75 nM or 30 ng/ml). (Louis, MO, USA). The active Vitamin D modulates the T-cell phenotype and promotes the development of Tregs [106].

  • 5 micrograms available over the counter, there are concerns around the risk of excessive vitamin D levels, which can, in rare cases, cause side effects, including nausea and vomiting.
  • Latest studies have found no association between supplementation and disease activity and no changes in IFN signature in vitamin D deficient SLE patients (72, 73).
  • Low levels of vitamin D have also been associated with frequent infections.
  • This, in turn, would stimulate expression of VDR and sensitivity to 1,25D.
  • Another bone action of active Vitamin D is recruiting osteoclasts from the monocyte-macrophage lineage of cells [21].

Low vitamin D can be found in all ethnic and age groups, around the world, for a host of reasons. A study by Panda et al, an animal model of 1-α hydroxylase deficiency was used to investigate the effects of 1,25(OH)2D3 on immune function. The IL-6 receptor consists of two different polypeptide chains:

The active Vitamin D inhibit B cell proliferation and this is associated with apoptosis of both activated and dividing B cells. While, Vitamin D supplement must be ensured in high risk groups, however, there is no need to measure serum Vitamin D concentrations on healthy people [210]. The importance of Treg as a facet of vitamin D immunomodulation is illustrated by various studies in vivo. Talk to your healthcare provider. That's why people call it the sunshine vitamin. Dermatoendocrinol (2020) 5(3): The development of lymphocytes takes place in the thymus with VDR being expressed in medullary thymocytes but not in the less mature cortical thymocytes (Ravid et al. )

  • In the skin, cholecalciferol is synthesized from 7-dehydrocholesterol when exposed to UVB.
  • It is the gatekeeper to a constitutionally strong body.
  • However, research work showed that Vitamin D is a prohormone and it is established now that it has many other biologic actions outside the musculoskeletal system [1,2].
  • The potential for enhancing the effects of biologics with simple, low-risk addition of 1,25-(OH) 2 D3 is interesting, and further work is required to validate this initial in vitro finding.

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And since we are usually sitting in an office away from natural light or hiding from the negative effects of the sun—and our diets don’t deliver the vitamin D we need—supplementation might be our best chance to promote a healthy immune system. These “interactomes” provide a picture of the cooperativity of responses to a particular cell treatment. The exons 1A, 1B, and 1C are present in the noncoding 5-prime end and its translated product is encoded by 8 additional exons. Military recruits from Finland with low Vitamin D lost more days from active duty (i. )

This type of laboratory study helps researchers to unravel the complex events that occur in individual cells in the immune system. Get your vitamin D levels tested by your doctor if you suspect a deficiency. After organ transplants, T cells can attack the donor organ as a ‘foreign invader’. 362-71 Ginde AA, Liu MC, Camargo CA, Jr. Vitamin D deficiency during pregnancy has been linked to the development of childhood asthma, but most studies in this area have been observational.

  • In the following section, we have summarized the latest results associating vitamin D insufficiency and vitamin D supplementation in SLE.
  • To date, these studies have focused on cancer (Wang et al.)
  • However, these suppressive effects are attributed to vitamin D feedback mechanisms to reduce tissue damage [167].
  • Vitamin D 3 itself is biologically inactive.
  • Thus, cells of the immune system respond to vitamin D and also activate vitamin D in a paracrine or autocrine fashion.
  • Vd and Adaptive Immunity Activated T and B cells possess only the enzymatic activity for converting 25(OH)D3 to 1,25(OH) 2 D3 [32].

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1-Alpha-calcidol modulates major human monocyte antigens and toll-like receptors TLR 2 and TLR4 in vitro. Despite the immunomodulatory properties of VD, the beneficial role of VD supplementation as a component of RA treatment has produced inconsistent results [164–166]. However, for pathogens such as M. Many cereals and brands of milk are fortified with vitamin D, so this is a great option if you want to avoid taking supplements. The first step of formation of cholecalciferol (VD3) from 7-dehydrocholesterin takes place in the skin under the effect of UV irradiation, that is, sunshine. In UK, Vitamin D supplement of 400 IU/day was advised to be given on for people over 65 years old with the aim of achieving Vitamin D level about 20 ng/ml [207]. By contrast, induction of CAMP appears to be primarily dependent on binding of VDR to promoter VDRE (Liu et al. )In addition to observational studies, numerous randomized trials have addressed the question whether vitamin D levels are associated with the risk of developing autoimmunity and whether development and disease progression can be influenced by vitamin D supplementation.

In immune system cells, VDR is present on monocytes and macrophages, dendritic cells, T cells and B cells. Interestingly, 1-α-hydroxylase enzyme forms were also described in keratinocytes and consequently, they were considered as a source for autocrine synthesis of 1,25(OH) 2 D [11]. The active Vitamin D decreases the proliferation and inhibits the production of IL-2, IFN-γ, tumor necrosis factor-α and IL-5 from Th1 cells [97,99]. The researchers were especially interested in how much the cells produced a particular form of phospholipase C, called phospholipase C-γ1, and how this was linked to the presence of the vitamin D receptor.

Abou-Raya A, Abou-Raya S, Helmii M. In addition, cathelicidin promotes autophagy, which enhances auto-phagolysosomal fusion and antimicrobial activity. Combination of Vitamin D with RAAS blockades can ameliorate renal fibrosis [141]. Other studies have shown effects in cytokine profiles and T cell differentiation (74, 75). An intensive regimen of VD supplementation in SLE patients with inactive disease, showed to obtain sufficient levels of serum 25(OH)D, but no effect on disease activity or serology [72]. The precise mechanism by which vitamin D regulates Tregs is still somewhat controversial.


Vitamin D helps ensure that the body absorbs and retains calcium and phosphorus, both critical for building bone. The innate immune system is the immediate, non-specific first line of the defense against pathogens and includes complement, antimicrobial peptides produced by neutrophils and macrophages, in addition to antigen presentation [45]. Numerous other cell types can also produce TNFα, including fibroblast, monocytes, natural killer cells, and mast cells [59]. Another study conducted to find out the effect of VD on levels of proinflammatory cytokines found that VD significantly downregulated the levels of IL-1β [79]. The high expression of VDR by monocytes ensures sensitivity of these cells to the differentiating effects of active Vitamin D.

1 Vitamin D and the innate immune system

VD has also inhibitory effects on B cells and plasma-cells, reducing their proliferation, differentiation and Ig secretion. 40-80 ng/ml; high Normal: Also, the potential for confounding factors was investigated, since the presence of a systemic inflammatory response was reported to be associated with lower levels of micronutrients like albumin or lipid soluble vitamins, in plasma [19]. Genome-wide strategies have played a pivotal role in elucidating the core mechanisms that trigger the intracrine vitamin D system and associated immune responses in cells such as monocytes/macrophages and DCs. Vitamin D deficiency. In humans, vitamin D is mainly synthesized in the skin after exposure to UVB whereas only a minor part (<10%) is derived from dietary sources (7).

Holmlund-Suila E. Read more tips on her blog, Health in a Hurry! A correlation with severe nailfold video-capillaroscopic alterations and worse quality of life parameters were reported in patients with diffuse SSc form and with lower 25(OH)D serum concentrations [88].

Screening for disease-specific microRNAs will be particularly important to identify non-coding RNAs that can target components of the intracrine vitamin D. A similar cooperative TLR response has also been described for epithelial keratinocytes, where basal expression of CYP27B1 is insufficient to facilitate intracrine induction of antibacterial proteins by serum 25D. You also need vitamin D for other important body functions. Melatonin sleep aid supplement: effectiveness, dosage, & side effects, short-term melatonin administration reduces inflammation in a mouse model of colitis [13]. The authors cite evidence that those with at least 75 nmol/liter seem have to markers of stronger immune function and are less likely to contract respiratory infections. Adams), and AI073539 (Robert L. In the northern hemisphere, people who live in Boston (U. )Vitamin D may also help increase muscle strength, which in turn helps to prevent falls, a common problem that leads to substantial disability and death in older people.

2 Vitamin D and autoimmunity

Subsequent experiments in vitro support this hypothesis, with the Th1 cytokine IFNγ enhancing TLR2/1-induced vitamin D-activation and associated antibacterial activity (Edfeldt et al. )Similarly, another study showed that VD induced IL-1β production in lipopolysaccharide-treated human monocytes-derived macrophages and it also increased the production and phosphorylation of IL-1β transcriptional regulatory factor (C/EBPβ-CCAAT enhancer binding protein β) [78]. However, in recent studies, we have shown that T cells from synovial fluid of RA patients’ inflamed joints are relatively insensitive to 1,25-(OH) 2 D3, despite expressing the VDR machinery required for 1,25-(OH) 2 D3 signalling [153]. It can also be found in fish liver oil, eggs and fatty fish such as salmon, herring and mackerel or taken as a dietary supplement. An illuminating example of this strategy is provided by the disease leprosy which, like TB, involves a mycobacterial infection—in this case Mycobacterium leprae (M. Dr miriam stoppard: fasting presses the body’s reset switch and gets rid of damaged cells. )8 ng/ml) identified 31 genes that were differentially expressed >2-fold (p < 0. The levels of this cytokine are considerably elevated in the serum of RA patients [92–94].

There’s evidence that vitamin D plays a role in controlling blood pressure and preventing artery damage, and this may explain these findings.
This particular study also illustrates a key advantage of genome/proteome-wide analyses, which is the ability to group changes in gene/protein expression according to specific properties such as metabolism or cytoskeletal function.

Where Did The Story Come From?

Branscheidt M. One study found that insufficient levels of Vitamin D have been reported in 36% of healthy adolescents and 57% of adults in the U. Indeed, 1,25D is a potent inhibitor of T-cell proliferation, blocking the transition from early G1 phase to late G1 phase (Bhalla et al. )

VDR is an important element in host immune response to different infection. The findings, continues Professor Geisler, “could help us to contain infectious diseases and global epidemics. However, these studies were dependent on questionnaire for dietary Vitamin D intake and the serum levels of Vitamin D were not reported [179]. Consequently, there has been a revival of interest in the role of other vitamin D metabolites both in serum and disease-affected synovial fluid as potentially more informative markers for vitamin D function in RA. Initial experiments suggested that the most likely mechanism for this was an indirect effect through inhibition of Th cells (Lemire et al. )Genetic variation in the VDR gene has been linked to RA risk [37–40]. Subsequent functional studies confirmed that dose-dependent vitamin D induction of CAMP transcription involves direct interaction between liganded VDR and VDRE in the CAMP gene promoter (Wang et al. )

These patients are also commonly vitamin D-deficient (Zehnder et al. )Vitamin D in massive doses as an adjuvant to the sulfones in the treatment of tuberculoid leprosy. Indeed, accumulating evidence has shown that insufficient vitamin D levels may lead to dysregulation of immune responses, and thus contribute to autoimmune diseases. Several studies link low vitamin D levels with an increased risk of fractures in older adults, and they suggest that vitamin D supplementation may prevent such fractures—as long as it is taken in a high enough dose.


The active Vitamin D may induce the production of IL-10 via help to TGF-β via the generation of IL-27 [111]. Nearly 30 years ago, researchers noticed an intriguing relationship between colon cancer deaths and geographic location: The main objective is to assess the variation in plasma levels of cathelicidin before and after influenza vaccination. Thus, it inhibits the B cell proliferation by inhibiting the previous cycling B cells from entering the cell cycle. Measuring serum level of 25(OH)D is used currently to assess Vitamin D status, however, this will not provide enough information about Vitamin D endocrine function. Ways to boost your immune response and fight disease, greek yogurt is filled with sickness-fighting probiotics and is packed with more protein than regular yogurt. Calcitriol and its analogs are able to suppress DC differentiation (29) and maturation in vitro.

What isn’t known yet is how much vitamin D you need so there is enough calcitriol to maximize the way your immune system works.


The study, published in Frontiers in Immunology, was funded by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Natural Environment Research Council and Wellcome. This can be explained by stimulating expression of chemokine receptor 10 (CCR10) by active Vitamin D on T lymphocytes and the CCR10 recognizes the chemokine CCL27 secreted by epidermal keratinocytes [97]. After three months, the vitamin D levels of the children who drank the fortified milk reached 19 ng/ml, on average, while the other children's levels remained unchanged, according to the study published in the journal Pediatrics in August.

Not sure how to tell whether or not you're getting enough vitamin D? Active T cells multiply at an explosive rate and can create an inflammatory environment with serious consequences for the body. Deficiency in vitamin D is associated with increased autoimmunity and an increased susceptibility to infection. In mice with induced experimental autoimmune encephalomyelitis (EAE), oral administration of active Vitamin D reduces the number of lymphocytes especially CD4+ T cells in the central nervous system (CNS) [108]. L-lep lesions (Montoya et al. )Various cells of the immune system also express the VDR and harbor 1-α-hydroxylase [10, 11].

This genome-wide approach provided the first unbiased evidence of a role for vitamin D metabolism and signaling in innate immune responses to a pathogen. To evade this antibacterial process and maintain intracellular viability M. Some even argue that vested interests are propping up the billion-dollar vitamin industry, with Spector calling vitamin D supplements a “pseudo-vitamin for a pseudo-disease”. 10 tips for building a strong immune system, specifically, a 2020 review of 17 studies found that taking zinc supplements within 24 hours of the onset of symptoms reduces the duration of common cold symptoms. For the research team, identifying the role of vitamin D in the activation of T cells has been a major breakthrough.

In common with natural killer cells (NK) and cytotoxic T-lymphocytes (cytotoxic T-cells), macrophages and their monocyte precursors play a central role in initial non-specific immune responses to pathogenic organisms or tissue damage-so called cell-mediated immunity.

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To clarify the role of the TLR2/1 heterodimer in mediating innate immune responses to the TB pathogen, Mycobacterium tuberculosis (M. )Therefore, the availability of sufficient level of Vitamin D represents an exogenous and endogenous player in AIDs [175]. The kidney is the major organ involved in the formation of bioactive forms of Vitamin D and is the major target organ (VDR is highly expressed) for the classical and non-classical actions of Vitamin D. Evidence is also emerging that vitamin D may augment certain therapies in RA. It is also unclear what effect, if any, viral pathogens such as hepatitis C or HIV have on innate and adaptive immune actions of vitamin D, although HIV infection of some cells has been shown to suppress expression of VDR (Chandel et al. )Serum 25(OH)D is considered as the most accurate marker for vitamin D. The assumption is that this mechanism will be potently activated by the relatively high circulating levels of 25D and 1,25D that are characteristic of non-human primates (Adams et al. )Vitamin D forms in our skin in response to sunlight, but care should still be taken to avoid burning or over-exposure.

IL-10 is known to down-regulate inflammatory responses reducing antigen presentation by DCs and macrophages [28]. However, they also identified important differences between patient subgroups, including a stronger inverse relationship between RA disease activity and serum 25-OHD3 in studies from developing countries, and in low-latitude climates. In animal models of experimental autoimmune encephalitis (the most widely used mouse model of MS), IBD and T1D, 1,25-(OH) 2 D3 promotes a Treg phenotype and augment IL-10 production, thus inhibiting Th17 responses and ameliorating disease [54]. 1–6 For example, one research study analyzed nearly 11,000 participants (that’s a lot of people!) However, it is important to recognize that the effect of vitamin D on serum levels of hepcidin may have additional consequences that are both positive (suppression of anemia) and negative (decreased hepcidin for systemic infection). Can masturbation help prevent covid-19? 1 Plus, another study showed that a high dose of garlic extract can the amount of cold or flu sick days by 61%. Binge drinking can also impair the immune system. Due to the immunomodulatory effect of VD on Th17 cells, it was found that active form of VD decreases the production of Th17 from CD4+T cells in humans and also it cuts down the expression of IL-17 in CD4+ T cells [105].

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In addition, vitamin D exerts effects that oppose the effect of IL-4 on MHC class II antigen expression in human monocytes and specifically modulates human monocyte phenotype and function by altering HLA-DR expression and antigen presentation, leaving lytic function intact (33). 10 ways to support your pet’s immune system, arginine is known to aid in wound healing, kidney function, and maintaining strong immune and hormonal systems. In the study, the Authors observed that VD plasmatic concentrations, age and an autoimmune rheumatic disease, were independent predictors for hyperparathyroidism. Two of these sub-groups, Th 1 (IL-2, IFNγ, tumor necrosis factor alpha) and Th 2 (IL-3, IL-4, IL-5, IL-10) T cells, respectively support cell-mediated and humoral immunity (Abbas et al. )Expression of 5-LO in human monocytes is induced by both 1,25D and TGFβ (Harle et al. )The saying goes “you are what you eat,” but in reality, “you are what you absorb. Vitamin D, reactive oxygen species and calcium signalling in ageing and disease. Vitamin D supplementation in low/moderate doses is not thought to be harmful to patients, has wider health benefits, is relatively inexpensive and has fewer side effects/interactions compared with many other commonly used treatments for RA, such as non-steroidal anti-inflammatory drugs (NSAIDs), or conventional synthetic or biological disease-modifying anti-rheumatic drugs (DMARDs).

Article Info

The VDR gene is located on chromosome 12 and is a member of trans-acting transcriptional regulatory factors that include the steroid and thyroid hormone receptors [35]. In the long term, some studies suggest too much vitamin D can increase risk of cardiovascular disease, although the research isn’t conclusive. This is mainly synthesized by activated macrophages. An essential point in this series is the interaction of VDR with retinoid X receptor (RXR) forming a heterodimeric complex that binds to specific DNA sequence elements [vitamin D response element (VDREs)] in vitamin D-responsive genes.

Materials And Methods

It’s still a matter of scientific debate. The human body can synthesize VD under the exposure of β-radiations and UV light or can absorb it through food. The best immune boosting supplements, vaccines teach the immune system to recognize specific pathogens and prepare them to mount a defense if they are encountered. VD plays a vital part in the regulation of various immunity mediated responses [44].

T and B cells express VDR and are important target cells of calcitriol immune regulation. Vitamin D deficiency is very important health problem because it affects many biological activities and bone mineralization. J Rheumatol (2020) 40(3): The active form of vitamin D tempers the damaging inflammatory response of some white blood cells, while it also boosts immune cells’ production of microbe-fighting proteins.