Experimental autoimmune encephalomyelitis in the common marmoset: a translationally relevant model for the cause and course of multiple sclerosis

Hart, Bert A. ’t

doi:10.5194/pb-6-17-2019

Cited by 12 publications

(3 citation statements)

References 222 publications

(282 reference statements)

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“…Various lines of evidence suggest that the two processes (systemic and central inflammaging) are related and interdependent 13 , 14 . For example, experimentally induced systemic inflammation (e.g., endotoxin administration) has effects on the brain in both rodents and primates 15 , 16 . These effects may be mediated by direct signaling through vagal afferents, through cytokines in the circulation that signal across the blood-brain barrier, or by immune cells infiltrating the brain.…”

Section: Introductionmentioning

confidence: 99%

CCR3 plays a role in murine age-related cognitive changes and T-cell infiltration into the brain

Rege¹,

Teichert²,

Masumi³

et al. 2023

Commun Biol

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Targeting immune-mediated, age-related, biology has the potential to be a transformative therapeutic strategy. However, the redundant nature of the multiple cytokines that change with aging requires identification of a master downstream regulator to successfully exert therapeutic efficacy. Here, we discovered CCR3 as a prime candidate, and inhibition of CCR3 has pro-cognitive benefits in mice, but these benefits are not driven by an obvious direct action on central nervous system (CNS)-resident cells. Instead, CCR3-expressing T cells in the periphery that are modulated in aging inhibit infiltration of these T cells across the blood-brain barrier and reduce neuroinflammation. The axis of CCR3-expressing T cells influencing crosstalk from periphery to brain provides a therapeutically tractable link. These findings indicate the broad therapeutic potential of CCR3 inhibition in a spectrum of neuroinflammatory diseases of aging.

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Section: Introductionmentioning

confidence: 99%

CCR3 plays a role in murine age-related cognitive changes and T-cell infiltration into the brain

Rege¹,

Teichert²,

Masumi³

et al. 2023

Commun Biol

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“…In rodent EAE, it has also been reported that IL-17-deficient mice have a less severe disease than wild-type mice ( 39 ), and that IL-17 worsened EAE in mice ( 40 ). In EAE in marmosets, it was found that treatment with an anti-IL-17A antibody induced a moderate delay of clinical scores, without abrogating EAE development ( 41 ). Th17 have often been associated with demyelinating diseases in children and adults, such as MS ( 42 , 43 ) and MOGAD ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Regulatory T Cells Increase After rh-MOG Stimulation in Non-Relapsing but Decrease in Relapsing MOG Antibody-Associated Disease at Onset in Children

et al. 2021

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BackgroundMyelin oligodendrocytes glycoprotein (MOG) antibody-associated disease (MOGAD) represent 25% of pediatric acquired demyelinating syndrome (ADS); 40% of them may relapse, mimicking multiple sclerosis (MS), a recurrent and neurodegenerative ADS, which is MOG-Abs negative.AimsTo identify MOG antigenic immunological response differences between MOGAD, MS and control patients, and between relapsing versus non-relapsing subgroups of MOGAD.MethodsThree groups of patients were selected: MOGAD (n=12 among which 5 relapsing (MOGR) and 7 non-relapsing (MOGNR)), MS (n=10) and control patients (n=7). Peripheral blood mononuclear cells (PBMC) collected at the time of the first demyelinating event were cultured for 48 h with recombinant human (rh)-MOG protein (10 μg/ml) for a specific stimulation or without stimulation as a negative control. The T cells immunophenotypes were analyzed by flow cytometry. CD4+ T cells, T helper (Th) cells including Th1, Th2, and Th17 were analyzed by intracellular staining of cytokines. Regulatory T cells (Tregs, Foxp3+), CD45RA-Foxp3+ Tregs and subpopulation naive Tregs (CD45RA+Foxp3int), effector Tregs (CD45RA-Foxp3high) and non-suppressive Tregs (CD45RA-Foxp3int) proportions were determined.ResultsThe mean onset age of each group, ranging from 9.9 to 13.8, and sex ratio, were similar between MOGR, MOGNR, MS and control patients as analyzed by one-way ANOVA and Chi-square test. When comparing unstimulated to rh-MOG stimulated T cells, a significant increase in the proportion of Th2 and Th17 cells was observed in MOGAD. Increase of Th17 cells was significant in MOGNR (means: 0.63 ± 0.15 vs. 1.36 ± 0.43; Wilcoxon-test p = 0.03) but not in MOGR. CD4+ Tregs were significantly increased in MOGNR (means: 3.51 ± 0.7 vs. 4.59 ± 1.33; Wilcoxon-test p = 0.046) while they decreased in MOGR. CD45RA-Foxp3+ Tregs were significantly decreased in MOGR (means: 2.37 ± 0.23 vs. 1.99 ± 0.17; paired t-test p = 0.021), but not in MOGNR. MOGR showed the highest ratio of effector Tregs/non suppressive-Tregs, which was significantly higher than in MOGNR.ConclusionsOur findings suggest that CD4+ Th2 and Th17 cells are involved in the pathophysiology of MOGAD in children. The opposite response of Tregs to rh-MOG in MOGNR, where CD4+ Tregs increased, and in MOGR, where CD45RA-Foxp3+ Tregs decreased, suggests a probable loss of tolerance toward MOG autoantigen in MOGR which may explain relapses in this recurrent pediatric autoimmune disease.

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“…In recent decades, marmosets have emerged as critical nonhuman primate models for neuroscience research in a diverse array of fields, including visual processing, neurodegenerative disease (Parkinson’s), autoimmune-mediated inflammatory disorders (EAE/MS), language acquisition and development, social behavior, and many others [ 56 , 57 , 58 ]. Refinements to historical practices used in neuroscience research, such as water regulation, should be made for all marmosets engaged in this research in order to optimize welfare during use.…”

Section: Welfare Implications Of Research Use: Select Modelsmentioning

confidence: 99%

Review of Environmental and Health Factors Impacting Captive Common Marmoset Welfare in the Biomedical Research Setting

Burns

2023

Veterinary Sciences

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As a small-bodied neotropical nonhuman primate species, common marmosets have unique requirements for adequate husbandry and veterinary care to ensure proper maintenance and to promote good animal welfare in a biomedical research setting. Environmental conditions, as well as medical and research-related manipulations, can impact marmoset welfare. Research focus areas, including basic neuroscience, transgenics, and aging, involve additional implications for marmoset welfare. This manuscript provides a comprehensive review of factors that should be considered and mitigated as needed by clinical and research staff working with marmosets in biomedical research facilities to optimize the welfare of captive marmosets.

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Experimental autoimmune encephalomyelitis in the common marmoset: a translationally relevant model for the cause and course of multiple sclerosis

Cited by 12 publications

References 222 publications

CCR3 plays a role in murine age-related cognitive changes and T-cell infiltration into the brain

CCR3 plays a role in murine age-related cognitive changes and T-cell infiltration into the brain

Regulatory T Cells Increase After rh-MOG Stimulation in Non-Relapsing but Decrease in Relapsing MOG Antibody-Associated Disease at Onset in Children

Review of Environmental and Health Factors Impacting Captive Common Marmoset Welfare in the Biomedical Research Setting

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