Search results for "experimental autoimmune encephalomyelitis"
showing 10 items of 88 documents
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…
Elevated NKG2D ligand expression in experimental autoimmune encephalomyelitis
2014
T cells remain unclear. Expressing myelin-reactive T cell receptor (TCR) is not sufficient to make a T cell encephalitogenic. In fact, the frequencies of myelin-reactive T cells are comparable between MS patients and healthy individuals, but the ones in MS patients have activated/memory phenotypes. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), myelin-specific T cells activated with antigen presenting cells (APCs) plus myelin peptide are encephalitogenic, whereas T cells activated with anti-CD3/CD28 antibodies are not. This suggests that APCs provide critical cytokines beyond T cell receptor activation and co-stimulation, contributing to encephalitogenicity. To …
The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis.
2019
Th17 cells, known as a highly pro-inflammatory subtype of Th cells, are involved very early in numerous aspects of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) neuropathology. A crucial event for the formation and accumulation of MS lesions is represented by the disruption of the blood brain barrier (BBB) in relapsing-remitting MS. Th17 cells also contribute to the progression of MS/EAE. These events will allow for the passage of inflammatory cells into the brain. Secondary to this, increased recruitment of neutrophils occurs, followed by increased protease activity that will continue to attract macrophages and monocytes, leading to brain inflammation with sus…
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…
Derivatives of Erythropoietin That Are Tissue Protective But Not Erythropoietic
2004
Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype–selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyeli…
Modulation of Neurological Deficits and Expression of Glutamate Receptors during Experimental Autoimmune Encephalomyelitis after Treatment with Selec…
2013
The aim of our investigation was to characterize the role of group I mGluRs and NMDA receptors in pathomechanisms of experimental autoimmune encephalomyelitis (EAE), the rodent model of MS. We tested the effects of LY 367385 (S-2-methyl-4-carboxyphenylglycine, a competitive antagonist of mGluR1), MPEP (2-methyl-6-(phenylethynyl)-pyridine, an antagonist of mGluR5), and the uncompetitive NMDA receptor antagonists amantadine and memantine on modulation of neurological deficits observed in rats with EAE. The neurological symptoms of EAE started at 10-11 days post-injection (d.p.i.) and peaked after 12-13 d.p.i. The protein levels of mGluRs and NMDA did not increase in early phases of EAE (4 d.p…
Mouse models for multiple sclerosis: historical facts and future implications.
2011
AbstractMultiple sclerosis (MS) is an inflammatory and demyelinating condition of the CNS, characterized by perivascular infiltrates composed largely of T lymphocytes and macrophages. Although the precise cause remains unknown, numerous avenues of research support the hypothesis that autoimmune mechanisms play a major role in the development of the disease. Pathologically similar lesions to those seen in MS can be induced in laboratory rodents by immunization with CNS-derived antigens. This form of disease induction, broadly termed experimental autoimmune encephalomyelitis, is frequently the starting point in MS research with respect to studying pathogenesis and creating novel treatments. M…
A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis.
2019
Precision therapy for immune tolerance Autoimmune diseases, such as multiple sclerosis (MS), result from a breach of immunological self-tolerance and tissue damage by autoreactive T lymphocytes. Current treatments can cause systemic immune suppression and side effects such as increased risk of infections. Krienke et al. designed a messenger RNA vaccine strategy that lacks adjuvant activity and delivers MS autoantigens into lymphoid dendritic cells. This approach expands a distinct type of antigen-specific effector regulatory T cell that suppresses autoreactivity against targeted autoantigens and promotes bystander suppression of autoreactive T cells against other myelin-specific autoantigen…
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…