Association of myelin peptide with vitamin D prevents autoimmune encephalomyelitis development

Mimura, Luiza Ayumi Nishiyama; Chiuso-Minicucci, Fernanda; Fraga-Silva, Thais F. C.; Zorzella-Pezavento, Sofia Fernanda Gonçalves; França, Thaís Graziela Donegá; Ishikawa, Larissa Lumi Watanabe; Penitenti, Marcimara; Ikoma, Maura Rosane Valério; Sartori, Alexandrina

doi:10.1016/j.neuroscience.2015.12.053

Cited by 23 publications

(16 citation statements)

References 44 publications

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“…Interestingly, the stabilization of this barrier coincided with a clear accumulation of MOG-reactive cells at the draining lymph nodes, which was detected by the increased production of proinflammatory cytokines by these cells in the presence of MOG. This finding is in contrast with the downmodulatory effect of vitamin D in cytokine production by spleen cells from normal mice (Mimura et al, 2016;Missio et al, 2018). A possible explanation for these findings is that vitamin D effects are distinct in normal and EAE conditions.…”

Section: Discussionmentioning

confidence: 84%

“…Previous findings from our group indicated that 1,25dihydroxyvitamin D3 (1,25-VitD3) has a protective effect when given alone or in combination with the specific autoantigen (myelin oligodendrocyte glycoprotein-MOG) (Chiuso-Minicucci et al, 2015;Mimura et al, 2016). Nonetheless, relevant information concerning the local immunopathogenic changes controlled by an early vitamin D administration remains lacking.…”

Section: Introductionmentioning

confidence: 99%

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Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation

et al. 2020

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Multiple sclerosis (MS) is a progressive disease of the central nervous system (CNS) that involves damage to the myelin sheath surrounding axons. MS therapy is based on immunomodulatory drugs that reduce disease recurrence and severity. Vitamin D is a hormone whose immunomodulatory ability has been widely demonstrated, including in experimental autoimmune encephalomyelitis (EAE), which is an animal model of CNS inflammation. In this study, we evaluated the potential of very early intervention with the active form of vitamin D (1,25-dihydroxyvitamin D3) to control neuroinflammation during EAE development. EAE was induced in C57BL/6J mice and 1,25-dihydroxyvitamin D3 administration began 1 day after disease induction. This procedure decreased prevalence, clinical score, inflammation, and demyelination. It also reduced MHCII expression in macrophages and microglia as well as the level of oxidative stress and messenger RNA (mRNA) expression for NLRP3, caspase-1, interleukin (IL)-1b, CX 3 CR1, CCL17, RORc and Tbx21 at the CNS. Otherwise, mRNA expression for ZO-1 increased at the lumbar spinal cord. These effects were accompanied by the stabilization of blood-spinal cord barrier permeability. The results of this study indicate that early intervention with 1,25-dihydroxyvitamin D3 can control the neuroinflammatory process that is the hallmark of EAE and MS immunopathogenesis and should thus be explored as an adjunct therapy for MS patients.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation

et al. 2020

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“…Vaccination with MOG associated with VitD, before EAE induction in C57BL/6 female mice, determined a significant clinical improvement characterized by absence of clinical score and no body weight loss. An impressive reduction in CNS inflammation, DC maturation and also cytokine production by CNS and spleen cell cultures was detected in these vaccinated animals [132]. As described in Section 6 of this chapter, this combination of MOG with VitD was also very efficient as a therapeutic procedure in the EAE model.…”

Section: Prophylactic Effect Of Vitd On Eaementioning

confidence: 65%

Therapeutic and Prophylactic Potential of Vitamin D for Multiple Sclerosis

Zorzella-Pezavento¹,

Ishikawa²,

Fraga-Silva³

et al. 2017

A Critical Evaluation of Vitamin D - Clinical Overview

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A plethora of investigations demonstrated that vitamin D (VitD) has a broad immunomodulatory potential. It induces tolerogenic dendritic cells in vitro leading to the development of regulatory T cells that have a key role in immunomodulation of autoimmune diseases including multiple sclerosis (MS). Studies showed that many MS patients present lower serum levels of VitD than healthy subjects. In addition, VitD supplementation has been associated with a reduced relative risk of developing MS. Considering the alterations in VitD levels in patients and also the immunomodulatory properties of VitD, it would be interesting to evaluate VitD potential as a tolerogenic adjuvant in experimental models of MS. In this context, our research team has been investigating strategies employing VitD to establish an in vivo tolerance state toward central nervous system antigens in experimental autoimmune encephalomyelitis (EAE). We observed that the association between a myelin peptide and VitD determined both therapeutic and prophylactic effects on EAE development.

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“…Mononuclear cells infiltrated in the CNS were obtained as previously described by Mimura et al, 2016 [38]. Briefly, sedated (ketamine/xylazine) mice were perfused with saline solution and then brain and the whole spinal cord were collected, macerated, resuspended in RPMI medium (Sigma Aldrich) supplemented with 2.5% collagenase D (Roche Applied Science) and incubated at 37°C, 5% CO 2 incubator for 45 min.…”

Section: Methodsmentioning

confidence: 99%

pVAXhsp65 Vaccination Primes for High IL-10 Production and Decreases Experimental Encephalomyelitis Severity

Zorzella-Pezavento

Chiuso-Minicucci

França

et al. 2017

Journal of Immunology Research

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Experimental autoimmune encephalomyelitis (EAE) is a demyelinating pathology of the central nervous system (CNS) used as a model to study multiple sclerosis immunopathology. EAE has also been extensively employed to evaluate potentially therapeutic schemes. Considering the presence of an immune response directed to heat shock proteins (hsps) in autoimmune diseases and the immunoregulatory potential of these molecules, we evaluated the effect of a previous immunization with a genetic vaccine containing the mycobacterial hsp65 gene on EAE development. C57BL/6 mice were immunized with 4 pVAXhsp65 doses and 14 days later were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein (MOG35–55) emulsified in Complete Freund's Adjuvant. Vaccinated mice presented significant lower clinical scores and lost less body weight. MOG35–55 immunization also determined less inflammation in lumbar spinal cord but did not change CD4+CD25+Foxp3+ T cells frequency in spleen and CNS. Infiltrating cells from the CNS stimulated with rhsp65 produced significantly higher levels of IL-10. These results suggest that the ability of pVAXhsp65 vaccination to control EAE development is associated with IL-10 induction.

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Association of myelin peptide with vitamin D prevents autoimmune encephalomyelitis development

Cited by 23 publications

References 44 publications

Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation

Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation

Therapeutic and Prophylactic Potential of Vitamin D for Multiple Sclerosis

pVAXhsp65 Vaccination Primes for High IL-10 Production and Decreases Experimental Encephalomyelitis Severity

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