Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immunoregulatory effects and therapeutic potential of vitamin D in multiple sclerosis.

ABSTRACT: Initially recognised as an important factor for bone health, vitamin D is now known to have a range of effects on the immune system. Vitamin D deficiency is associated with an increased risk of multiple sclerosis (MS), a chronic immune-mediated demyelinating disease of the CNS. In this review, we explore the links between vitamin D deficiency, MS risk, and disease activity. We also discuss the known immune effects of vitamin D supplementation and the relevance of these observations to the immunopathology of MS. Finally, we review the existing evidence for vitamin D supplementation as an MS therapy, highlighting several recent clinical studies and trials.

SUBMITTER: Yeh WZ

PROVIDER: S-EPMC7443468 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Immunoregulatory effects and therapeutic potential of vitamin D in multiple sclerosis.

Yeh Wei Zhen WZ Gresle Melissa M Jokubaitis Vilija V Stankovich Jim J van der Walt Anneke A Butzkueven Helmut H

British journal of pharmacology 20200805 18

Initially recognised as an important factor for bone health, vitamin D is now known to have a range of effects on the immune system. Vitamin D deficiency is associated with an increased risk of multiple sclerosis (MS), a chronic immune-mediated demyelinating disease of the CNS. In this review, we explore the links between vitamin D deficiency, MS risk, and disease activity. We also discuss the known immune effects of vitamin D supplementation and the relevance of these observations to the immuno ...[more]

PMID: 32668009

Similar Datasets

Interferon beta and vitamin D synergize to induce immunoregulatory receptors on peripheral blood monocytes of multiple sclerosis patients.

Project description:Immunoglobulin-like transcript (ILT) 3 and 4 are inhibitory receptors that modulate immune responses. Their expression has been reported to be affected by interferon, offering a possible mechanism by which this cytokine exerts its therapeutic effect in multiple sclerosis, a condition thought to involve excessive immune activity. To investigate this possibility, we measured expression of ILT3 and ILT4 on immune cells from multiple sclerosis patients, and in post-mortem brain tissue. We also studied the ability of interferon beta, alone or in combination with vitamin D, to induce upregulation of these receptors in vitro, and compared expression levels between interferon-treated and untreated multiple sclerosis patients. In vitro interferon beta treatment led to a robust upregulation of ILT3 and ILT4 on monocytes, and dihydroxyvitamin D3 increased expression of ILT3 but not ILT4. ILT3 was abundant in demyelinating lesions in postmortem brain, and expression on monocytes in the cerebrospinal fluid was higher than in peripheral blood, suggesting that the central nervous system milieu induces ILT3, or that ILT3 positive monocytes preferentially enter the brain. Our data are consistent with involvement of ILT3 and ILT4 in the modulation of immune responsiveness in multiple sclerosis by both interferon and vitamin D.

| S-EPMC4281069 | biostudies-literature

Therapeutic Role of Vitamin D in Multiple Sclerosis: An Essentially Contested Concept.

Project description:Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the nervous system with incredibly intricate etiopathogenesis involving numerous genetic, epigenetic, and environmental risk factors. Major environmental risk factors include ultraviolet (UV) radiation, vitamin D, Epstein-Barr virus (EBV) infection, smoking, and high body mass index (BMI). Vitamin D, in particular, can be viewed as one piece of this puzzle, with various tabs and pockets, occupying a sequential site. In this article, we have briefly discussed the neuroimmunology of MS and the role of vitamin D in regulating immune responses. Various observational studies and clinical trials were reviewed and discussed according to stages of disease activity and course of the disease. The data reviewed in this article implied that serum vitamin D levels greatly influence the risk of developing MS and disease activity. Long-term follow-up studies indicated that low serum vitamin D levels correlate with worse disability outcomes. Since clinical trials did not provide significant evidence, the role of vitamin D in controlling disease activity remains unresolved. Larger clinical trials are needed to support the findings of observational studies and provide significant evidence in favour of vitamin D.

| S-EPMC9311493 | biostudies-literature

Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications.

Project description:Vitamin D deficiency has been associated with the risk of multiple sclerosis, disease activity and progression. Results from in vitro experiments, animal models and analysis of human samples from randomized controlled trials provide comprehensive data illustrating the pleiotropic actions of Vitamin D on the immune system. They globally result in immunomodulation by decreasing differentiation of effector T and B cells while promoting regulatory subsets. Vitamin D also modulates innate immune cells such as macrophages, monocytes and dendritic cells, and acts at the level of the blood-brain barrier reducing immune cell trafficking. Vitamin D exerts additional activity within the central nervous system reducing microglial and astrocytic activation. The immunomodulatory role of Vitamin D detected in animal models of multiple sclerosis has suggested its potential therapeutic use for treating multiple sclerosis. In this review, we focus on recent published data describing the biological effects of Vitamin D in animal models of multiple sclerosis on immune cells, blood-brain barrier function, activation of glial cells and its potential neuroprotective effects. Based on the current knowledge, we also discuss optimization of therapeutic interventions with Vitamin D in patients with multiple sclerosis, as well as new technologies allowing in-depth analysis of immune cell regulations by vitamin D.

| S-EPMC9260308 | biostudies-literature

Vitamin D as a Potential Therapy for Multiple Sclerosis: Where Are We?

Project description:Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and is caused by an aberrant immune response to myelin sheath. Disease-modifying medications, which mainly aim to suppress such aberrant immune response, have significantly improved MS treatment. However, the disease severity continues to worsen. In contrast, progressively more data suggest that 1,25-dihydroxyvitamin D or 1,25(OH)2D, i.e., the active vitamin D, suppresses the differentiation of potentially pathogenic T cells associated with MS, enhances the differentiation of regulatory T cells that suppress the pathogenic T cells, and promotes remyelination. These novel 1,25(OH)2D functions have encouraged investigators to develop vitamin D as a potential therapy for MS. However, because of the hypercalcemia that is associated with high 1,25(OH)2D concentrations, supplementation of native vitamin D has been a major focus in clinical trials for the treatment of MS, but such trials have produced mixed data. In this article, we will review current progress in the supplementation of different vitamin D forms for the treatment of experimental autoimmune encephalomyelitis (i.e., an MS animal model) as well as MS. Furthermore, we will review alternative strategies that our laboratory and others are pursuing in an attempt to circumvent the hurdles that are hampering the effective use of vitamin D as a potential therapy for MS.

| S-EPMC7247155 | biostudies-literature

Variants within the immunoregulatory CBLB gene are associated with multiple sclerosis.

Project description:A genome-wide association scan of approximately 6.6 million genotyped or imputed variants in 882 Sardinian individuals with multiple sclerosis (cases) and 872 controls suggested association of CBLB gene variants with disease, which was confirmed in 1,775 cases and 2,005 controls (rs9657904, overall P = 1.60 x 10(-10), OR = 1.40). CBLB encodes a negative regulator of adaptive immune responses, and mice lacking the ortholog are prone to experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis.

| S-EPMC3786343 | biostudies-literature

The therapeutic potential of exercise for improving mobility in multiple sclerosis.

Project description:Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation and demyelination in the central nervous system (CNS) with subsequent axonal and neuronal degeneration. These changes are associated with a broad range of symptoms including skeletal muscle dysfunction. Importantly, musculoskeletal impairments manifest in various ways, compromise the quality of life and often precede the later development of mobility disability. As current standard disease modifying therapies for MS predominantly act on neuroinflammation, practitioners and patients face an unmet medical need for adjunct therapies specifically targeting skeletal muscle function. This review is intended to detail the nature of the skeletal muscle dysfunctions common in people with MS (pwMS), describe underlying intramuscular alterations and outline evidence-based therapeutic approaches. Particularly, we discuss the emerging role of aerobic and resistance exercise for reducing the perception of fatigue and increasing muscle strength in pwMS. By integrating the most recent literature, we conclude that both exercise interventions should ideally be implemented as early as possible as they can address MS-specific muscle impairments. Aerobic exercise is particularly beneficial for pwMS suffering from fatigue and metabolic impairments, while resistance training efficiently counters muscle weakness and improves the perception of fatigue. Thus, these lifestyle interventions or possible pharmacological mimetics have the potential for improving the general well-being and delaying the functional declines that are relevant to mobility.

| S-EPMC11427913 | biostudies-literature

Vitamin K2 in multiple sclerosis patients.

Project description:BACKGROUND:Vitamin K2 (VK2) belongs to the vitamin K family and comprises a number of subtypes differing in length of side chains consisting of isoprenoid groups (menaquinone-n, MK-n). It is essential for a number of physiological functions although the full spectrum of activity has not yet been elucidated. Due to its role in protection of mitochondrial damage, VK2 could be relevant in preventing disease progress in multiple sclerosis (MS). METHODS:We measured VK2 serum levels by the double antibody sandwich Enzyme-linked Immunosorbent Assay (ELISA) technique in MS patients and age and sex matched controls, both under vitamin D supplementation, and related it to disease characteristics and treatment. RESULTS:Overall, 45 MS patients (31 females and 39 of the relapsing-remitting type) and 29 healthy controls (19 females) were included in the analysis. The MS patients had vastly lower VK2 blood levels than controls (235 ± 100 ng/ml vs. 812 ± 154 ng/ml, respectively). Female patients had significantly lower VK2 levels than males and a decrease with age by approximately 10% per decade was found. The VK2 levels were lower with increasing numbers of attacks per year and were higher in patients with optic nerve lesions. No consistent relationship with medications was detected. CONCLUSION:The substantially lower levels of VK2 in MS patients could be due to depletion, lower production in the gut, diminished absorption or, less likely, reduced intake of precursor vitamin K1. The role of VK2 in MS development and progress deserves further study.

| S-EPMC5966473 | biostudies-literature

Role of inflammasomes in multiple sclerosis and their potential as therapeutic targets.

Project description:Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), and it remains the most common immune-mediated disorder affecting the CNS. While the cause of MS is unclear, the underlying pathomechanisms are thought to be either destruction by autoimmune T cells or dysfunction of myelin-producing cells. Recent advances have indicated that inflammasomes contribute the etiology of MS. Inflammasomes are multiprotein complexes of the innate immune response involved in the processing of caspase-1, the activation of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 as well as the cell death-mediated mechanism of pyroptosis and the activation of the adaptive immune response. Here we review the literature to date on the role of different inflammasome signaling pathways in the pathogenesis of MS and how these pathways may be targeted to reduce deleterious inflammatory processes and improve outcomes in this patient population.

| S-EPMC7469327 | biostudies-literature

Transcriptomics identifies blunted immunomodulatory effects of vitamin D in people with multiple sclerosis.

Project description:Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). However, the immune effects of vitamin D in people with MS are not well understood. We analyzed transcriptomic datasets generated by RNA sequencing of immune cell subsets (CD4+, CD8+ T cells, B cells, monocytes) from 33 healthy controls and 33 untreated MS cases. We utilized a traditional bioinformatic pipeline and weighted gene co-expression network analysis (WGCNA) to determine genes and pathways correlated with endogenous vitamin D. In controls, CD4+ and CD8+ T cells had 1079 and 1188 genes, respectively, whose expressions were correlated with plasma 25-hydroxyvitamin D level (P < 0.05). Functional enrichment analysis identified association with TNF-alpha and MAPK signaling. In CD4+ T cells of controls, vitamin D level was associated with expression levels of several genes proximal to multiple sclerosis risk loci (P = 0.01). Genes differentially associated with endogenous vitamin D by case-control status were enriched in TNF-alpha signaling via NF-κB. WGCNA suggested a blunted response to vitamin D in cases relative to controls. Collectively, our findings provide further evidence for the immune effects of vitamin D, and demonstrate a differential immune response to vitamin D in cases relative to controls, highlighting a possible mechanism contributing to MS pathophysiology.

| S-EPMC10792011 | biostudies-literature

Multiple sclerosis cuprizone mouse model and vitamin D supplementation

Project description:Dietary supplementation of vitamin D is commonly recommended to patients with multiple sclerosis (MS). We investigated the effect of 1,25-dihydroxyvitamin-D3 (1,25-(OH)2D3) on the brain proteome in the cuprizone model during remyelination. Mice were demyelinated with dietary cuprizone for 7 weeks. The mice received intra-peritoneal injections of 1,25-(OH)2D3 or placebo twice a week, from week 6 and throughout week 10. Brain samples were taken after 7 weeks (demyelinated), after 8 weeks (1 week remyelination) and after 10 weeks (3 weeks of remyelination). The six experimental groups were labeled with TMT, mixed mode HPLC fractionation, and applied to LC-MS which enabled quantification of 5062 proteins with high confidence.

2017-08-16 | PXD002347 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data