Search results for "experimental autoimmune encephalomyelitis"
showing 10 items of 88 documents
In toxic demyelination oligodendroglial cell death occurs early and is FAS independent
2010
Oligodendroglial cell death is a frequent phenomenon of many neurological diseases, e.g. in demyelinating diseases such as multiple sclerosis (MS). The underlying mechanisms are largely unknown. Here, we demonstrate that in the toxic demyelination cuprizone model, oligodendroglial cell death and downregulation of myelin genes start days after initiation of the cuprizone diet and weeks before demyelination is obvious. In early – but not in later – stages, dying oligodendrocytes express activated caspase 3, suggesting a switch from classical apoptotic pathways to caspase 3-independent mechanisms during the course of the cuprizone diet. The expression level of FAS in the corpus callosum, a cel…
Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis.
2011
BackgroundIt is increasingly clear that some heat shock proteins (Hsps) play a role in inflammation. Here, we report results showing participation of Hsp60 in the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated by data from both in vivo and in vitro analyses.Methods and resultsBronchial biopsies from patients with stable COPD, smoker controls with normal lung function, and non-smoker controls were studied. We quantified by immunohistochemistry levels of Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, and HSF-1, along with levels of inflammatory markers. Hsp10, Hsp40, and Hsp60 were increased during progression of disease. We found also a positive correlation between th…
The role of NFATc2 in chronic autoimmune neuroinflammation
2014
Dimethyl fumarate (DMF), a fumaric acid ester with potential immunomodulatory and neuroprotective effect, was recently approved as treatment for relapsing–remitting multiple sclerosis (MS). DMF ameliorates the clinical course of experimental autoimmune encephalomyelitis (EAE), the murine model of MS, where it exerts a neuroprotective action, reducing demyelination and axonal loss. We hypothesized that these effects are mediated, at least in part, through its action on microglia. We used a microglial cell line (N9) activated with lipopolysaccharide (LPS) to analyze the effect of monomethyl fumarate (MMF), a bioactive metabolite of DMF, in vitro. We show that MMF reverts the molecular phenoty…
Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism
2015
The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK …
Unraveling the T-B tangle in anti-CD20 multiple sclerosis therapy.
2019
Significance Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. CD8+ T cells have been strongly implicated in MS pathogenesis, but it is unclear whether myelin is a CD8+ T cell autoantigenic target in MS. This study demonstrated that while myelin-specific CD8+ T cells are present at similar frequencies in untreated MS patients and healthy subjects, the proportion of memory and CD20-expressing myelin-specific CD8+ T cells was increased in MS patients, suggesting prior antigen encounter. This activated phenotype was reversible as the memory and CD20-expressing populations of certain myelin-specific CD8+ T cells were reduced following anti-CD20 trea…
Modeling a complex disease: Multiple sclerosis—Update 2020
2021
Multiple sclerosis (MS) is a complex inflammatory disease of the central nervous system (CNS) with an unknown etiology. Thereby, MS is not a uniform disease but rather represents a spectrum of disorders, where each aspect needs to be modeled with specific requirements-for a systematic overview see our previous issue of this review (Kurschus, Wortge, & Waisman, 2011). However, there is broad consensus about the critical involvement of the immune system in the disease pathogenesis. To better understand how the immune system contributes to CNS autoimmunity, the model of experimental autoimmune encephalomyelitis (EAE) was developed. EAE can be induced in susceptible animals in many different wa…
ID: 186
2015
In the past years, and clear pathogenic role was shown for Th17 cells in the development of autoimmune diseases. In particular, these cells were shown to play a critical roIn the past years, and clear pathogenic role was shown for Th17 cells in the development of autoimmune diseases. In particular, these cells were shown to play a critical role in the development of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. One of the major cytokines Th17 cells produce is IL-17A, a cytokine of the IL-17 family. IL-17A, as well as it homologue IL-17F bind and trigger cells via the IL-17 receptor A/C complex. We have used a series of mice with deficiencies in the…
FRET based ratiometric Ca(2+) imaging to investigate immune-mediated neuronal and axonal damage processes in experimental autoimmune encephalomyeliti…
2015
Abstract Background Irreversible axonal and neuronal damage are the correlate of disability in patients suffering from multiple sclerosis (MS). A sustained increase of cytoplasmic free [Ca2+] is a common upstream event of many neuronal and axonal damage processes and could represent an early and potentially reversible step. New method We propose a method to specifically analyze the neurodegenerative aspects of experimental autoimmune encephalomyelitis by Forster Resonance Energy Transfer (FRET) imaging of neuronal and axonal Ca2+ dynamics by two-photon laser scanning microscopy (TPLSM). Results Using the genetically encoded Ca2+ sensor TN-XXL expressed in neurons and their corresponding axo…
Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling
2009
SummaryT helper (Th) 17 cells have been recently discovered in both mouse and human. Here we show that interleukin-1 (IL-1) signaling on T cells is critically required for the early programming of Th17 cell lineage and Th17 cell-mediated autoimmunity. IL-1 receptor1 expression in T cells, which was induced by IL-6, was necessary for the induction of experimental autoimmune encephalomyelitis and for early Th17 cell differentiation in vivo. Moreover, IL-1 signaling in T cells was required in dendritic cell-mediated Th17 cell differentiation from naive or regulatory precursors and IL-1 synergized with IL-6 and IL-23 to regulate Th17 cell differentiation and maintain cytokine expression in effe…
Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation
2009
Abstract The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell–derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17–producing T cel…