Persistent Inflammation in the CNS during Chronic EAE Despite Local Absence of IL-17 Production

Zorzella-Pezavento, Sofia Fernanda Gonçalves; Chiuso-Minicucci, Fernanda; França, Thaís Graziela Donegá; Ishikawa, Larissa Lumi Watanabe; Rosa, Larissa Camargo da; Marques, Carlo Aldrovandi Torreão; Ikoma, Maura Rosane Valério; Sartori, Alexandrina

doi:10.1155/2013/519627

Cited by 39 publications

(35 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effects of infiltrating cells on the CNS during the course of EAE depend on the release of cytokines and chemokines that are responsible for neuroinflammation [31]. In order to determine the inflammatory We found significant differences between CFA and EAE groups in IFN, TNF, IL-10 and IL-1 mRNA expression levels (Fig.…”

Section: Mecp2 308/y Mice Show Higher and Persisting Inflammatory Resmentioning

confidence: 95%

“…Myeloid cells are key for the onset and progression of EAE. These cells adopt different phenotypes that coexist in the CNS after MOG immunization, and the balance between these phenotypes and the immune mediators they release are essential for mantainance of the chronic phase [31]. Since it has been shown that MeCP2 is expressed in microglial cells and that its deletion can alter the lifespan and pathogenic phenotype in mice [32], we sought to evaluate the level of microgliosis after EAE-induction.…”

Section: Mecp2 Deficit Does Not Alter the Expression Of Iba1 And Micrmentioning

confidence: 99%

See 1 more Smart Citation

MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge: implications for Rett Syndrome

Zalosnik

Fabio

Bertoldi

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundRett syndrome is a severe and progressive neurological disorder linked to mutations in the MeCP2 gene located on the X chromosome. So far it has not been established how the presence of a mutant form of MeCP2 can maintain essential regulation of immune responses to support the normal homeostasis of individuals. Since MeCP2 is mostly expressed as a “partially functional” protein in humans with RTT, the aim of our work was to evaluate whether a mutation in MeCP2 interferes with the induction of neuroinflammatory responses in real time.MethodsWe used MeCP2308/y mouse model (MUT) and exposed it to an autoimmune challenge, experimental autoimmune encephalomyelitis (EAE). WT and MUT mice were immunized with CFA-MOG or CFA alone (control) and clinical scores were evaluated daily. Animals were sacrificed at either 12 days post-induction (dpi, acute stage) or 30 dpi (chronic stage) and spleen and spinal cord were collected from individual mice for further studies. Cellular infiltration and microgliosis was evaluated by IHC. Cytokine production was assessed in spinal cord and in cultured splenocytes after MOG activation ex-vivo by cytometry and real time RT-PCR.ResultsOur results showed that MeCP2 deficiency increased the susceptibility to develop EAE, along with a defective induction of anti-inflammatory responses and an exacerbated MOG-specific reactivity with high IFNγ expression in peripheral immune sites. During the chronic stage, an increase in gene expression of pro-inflammatory cytokines (IFNγ, TNFα and IL-1β) and downregulation of genes relevant for immune regulation (IL-10, FoxP3 and CX3CR1) was found in MUT-EAE spinal cords.ConclusionsThis is the first study performed in a MeCP2 mutant mouse model that explores the pathophysiology and neuroinflammation in the context of an autoimmune challenge. We could establish that an MeCP2 mutation act intrinsically affecting neuroimmune interactions by promoting an inflammatory environment and a deficient immune regulatory setting. These results are relevant for understanding the consequences of MeCP2 mutations on immune homeostasis in MeCP2-related disorders, as well as setting the bases for further therapeutic interventions that consider the immune status in patients.

show abstract

Section: Mecp2 308/y Mice Show Higher and Persisting Inflammatory Resmentioning

confidence: 95%

Section: Mecp2 Deficit Does Not Alter the Expression Of Iba1 And Micrmentioning

confidence: 99%

MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge: implications for Rett Syndrome

Zalosnik

Fabio

Bertoldi

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…EAE was induced as previously reported [37]. Briefly, mice were immunized with 150 μ g of MOG 35–55 emulsified in CFA containing 400 μ g of BCG.…”

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Animals that survive EAE recover in the period between the 30th and 40th days after the sensitization. Resensitization can induce the disease again with previously actively induced EAE, only by a passive transmission of the myelin antigen (Zorzella-Pezavento et al, 2013).…”

Section: Experimental Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 99%

Neuroinflammation and demyelination from the point of nitrosative stress as a new target for neuroprotection

Ljubisavljević¹,

Stojanović²

2015

Reviews in the Neurosciences

View full text Add to dashboard Cite

AbstractThe role of nitrosative stress in the early pathogenesis of neuroinflammation and demyelination is undoubtedly wide. This review summarizes and integrates the results, found in previously performed studies, which have evaluated nitrosative stress participation in neuroinflammation. The largest number of studies indicates that the supply of nitrosative stress inhibitors has led to the opposite clinical effects in experimental studies. Some results claim that attributing the protective role to nitric oxide, outside the total changes of redox oxidative processes and without following the clinical and paraclinical correlates of neuroinflammation, is an overrated role of this mediator. The fact is that the use of nitrosative stress inhibitors would be justified in the earlier phases of neuroinflammation. The ideal choice would be a specific inducible nitric oxide synthase (iNOS) inhibitor, because its use would preserve the physiological features of nitric oxide produced by the effects of constitutive NOS. This review discusses the antinitrosative therapy as a potential mode of therapy that aims to control neuroinflammation in early phases, delaying its later phases, which are accompanied with irreversible neurological disabilities. Some parameters of nitrosative stress might serve as surrogate biomarkers for neuroinflammation intensity and its radiological and clinical correlates.

show abstract

Persistent Inflammation in the CNS during Chronic EAE Despite Local Absence of IL-17 Production

Cited by 39 publications

References 49 publications

MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge: implications for Rett Syndrome

MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge: implications for Rett Syndrome

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

Neuroinflammation and demyelination from the point of nitrosative stress as a new target for neuroprotection

Contact Info

Product

Resources

About