Search results for "Myelin oligodendrocyte glycoprotein"

Role of the epigenetic factor Sirt7 in neuroinflammation and neurogenesis.

2017

Epigenetic regulators are increasingly recognized as relevant modulators in the immune and nervous system. The class of sirtuins consists of NAD+-dependent histone deacetylases that regulate transcription. Sirtuin family member Sirt1 has already been shown to influence the disease course in an animal model of autoimmune neuroinflammation (experimental autoimmune encephalomyelitis (EAE). A role of Sirt7, a related epigenetic regulator, on immune system regulation has been proposed before, as these mice are more susceptible to develop inflammatory cardiomyopathy. Sirt7-/- animals showed no differences in clinical score compared to wild-type littermates after EAE induction with myelin oligoden…

2018

In this study we analysed the effects of prophylactic biolistic DNA vaccination with plasmids encoding the encephalitogenic protein myelin oligodendrocyte glycoprotein (MOG) on the severity of a subsequently MOGp35-55-induced EAE and on the underlying immune response. We compared the outcome of vaccination with MOG-encoding plasmids alone or in combination with vectors encoding the regulatory cytokines IL-10 and TGF-s1, respectively. MOG expression was restricted to skin dendritic cells (DCs) by the use of the DC-specific promoter of the fascin1 gene (pFscn-MOG). For comparison, the strong and ubiquitously active CMV promoter was employed (pCMV-MOG), which allows MOG expression in all trans…

B7‐H1 and CD8+Treg: The enigmatic role of B7‐H1 in peripheral tolerance

2009

The interaction between B7-H1 (PD-L1) expressed on APC with PD-1 expressed by T cells was shown previously to result in inhibition of T-cell activation and autoimmune diseases. A paper in this issue of the European Journal of Immunology demonstrates that DC B7-H1 expression can in fact enhance autoimmunity, rather than suppress it. Using a model of direct injection of self antigen-loaded DC into the CNS, the authors demonstrate that DC with intact B7-H1 expression exacerbate CNS autoimmune disease. Importantly, the improved disease outcome in animals treated with B7-H1(-/-) DC is a result of a population of CD8(+) Treg cells that expand at the site of autoimmune inflammation.

Cross-recognition of a myelin peptide by CD8+ T cells in the CNS is not sufficient to promote neuronal damage.

2015

Multiple sclerosis (MS) is an inflammatory disease of the CNS thought to be driven by CNS-specific T lymphocytes. Although CD8+T cells are frequently found in multiple sclerosis lesions, their distinct role remains controversial because direct signs of cytotoxicity have not been confirmedin vivo. In the present work, we determined that murine ovalbumin-transgenic (OT-1) CD8+T cells recognize the myelin peptide myelin oligodendrocyte glycoprotein 40–54 (MOG40–54) bothin vitroandin vivo. The aim of this study was to investigate whether such cross-recognizing CD8+T cells are capable of inducing CNS damagein vivo. Using intravital two-photon microscopy in the mouse model of multiple sclerosis, …

A novel plasmid DNA electroporation method allows transfection of murine DC.

2007

Under steady state conditions dendritic cells (DC) exert tolerogenic function, but acquire potent immunogenic function due to strong upregulation of costimulatory molecules and proinflammatory cytokines. In numerous studies the potential of modified DC to induce tolerance or immune reactions towards a distinct antigen has been demonstrated. However, DC are refractory to transfection with plasmid DNA by non-viral methods. In this study we have tested the suitability of a newly developed electroporation device to transfect immature murine bone-marrow derived DC (BM-DC). Transfected BM-DC expressed reporter molecules at considerable extent which renders this method suitable to perform all kind…

In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis

2010

SummaryNeuronal damage in autoimmune neuroinflammation is the correlate for long-term disability in multiple sclerosis (MS) patients. Here, we investigated the role of immune cells in neuronal damage processes in animal models of MS by monitoring experimental autoimmune encephalomyelitis (EAE) by using two-photon microscopy of living anaesthetized mice. In the brainstem, we detected sustained interaction between immune and neuronal cells, particularly during disease peak. Direct interaction of myelin oligodendrocyte glycoprotein (MOG)-specific Th17 and neuronal cells in demyelinating lesions was associated with extensive axonal damage. By combining confocal, electron, and intravital microsc…

Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient KitW-sh/W-sh mice

2011

Mast cell (MC)-deficient c-Kit mutant Kit(W/W-v) mice are protected against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggesting a detrimental role for MCs in this disease. To further investigate the role of MCs in EAE, we took advantage of a recently characterized model of MC deficiency, Kit(W-sh/W-sh). Surprisingly, we observed that myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE was exacerbated in Kit(W-sh/W-sh) compared with Kit(+/+) mice. Kit(W-sh/W-sh) mice showed more inflammatory foci in the central nervous system (CNS) and increased T-cell response against myelin. To understand whether the discrepant results obtaine…

Apoptosis of oligodendrocytes via Fas and TNF-R1 is a key event in the induction of experimental autoimmune encephalomyelitis.

2005

Abstract In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, immunization with myelin Ags leads to demyelination and paralysis. To investigate which molecules are crucial for the pathogenesis of EAE, we specifically assessed the roles of the death receptors Fas and TNF-R1. Mice lacking Fas expression in oligodendrocytes (ODCs) were generated and crossed to TNF-R1-deficient mice. To achieve specific deletion of a loxP-flanked fas allele in ODCs, we generated a new insertion transgene, expressing the Cre recombinase specifically in ODCs. Fas inactivation alone as well as the complete absence of TNF-R1 protected mice partially from EAE induced by the imm…

Autoantibody depletion ameliorates disease in murine experimental autoimmune encephalomyelitis.

2013

Much data support a role for central nervous system antigen-specific antibodies in the pathogenesis of multiple sclerosis (MS). The effects of inducing a decrease in (auto)antibody levels on MS or experimental autoimmune encephalomyelitis (EAE) through specific blockade of FcRn, however, remain unexplored. We recently developed engineered antibodies that lower endogenous IgG levels by competing for binding to FcRn. These Abdegs ("antibodies that enhance IgG degradation") can be used to directly assess the effect of decreased antibody levels in inflammatory diseases. In the current study, we show that Abdeg delivery ameliorates disease in an EAE model that is antibody dependent. Abdegs could…

Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis

2008

T-cell recognition of autoantigens is important in the development of autoimmune disease. Now, Hartmut Wekerle and his colleagues demonstrate that organ-specific autoimmune responses may be driven by T cells that simultaneously respond to two different autoantigens found within the same target tissue. We describe here the paradoxical development of spontaneous experimental autoimmune encephalomyelitis (EAE) in transgenic mice expressing a myelin oligodendrocyte glycoprotein (MOG)-specific T cell antigen receptor (TCR) in the absence of MOG. We report that in Mog-deficient mice (Mog−/−), the autoimmune response by transgenic T cells is redirected to a neuronal cytoskeletal self antigen, neur…