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experimental autoimmune encephalomyelitis

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https://www.readbyqxmd.com/read/28543188/cd44-deletion-leading-to-attenuation-of-experimental-autoimmune-encephalomyelitis-results-from-alterations-in-gut-microbiome-in-mice
#1
Kumaraswamy Naidu Chitrala, Hongbing Guan, Narendra P Singh, Brandon Busbee, Alexa Gandy, Pegah Mehrpouya-Bahrami, Mitra S Ganewatta, Chuanbing Tang, Saurabh Chatterjee, Prakash Nagarkatti, Mitzi Nagarkatti
Dysbiosis in gut microbiome has been shown to be associated with inflammatory and autoimmune diseases. Previous studies from our laboratory demonstrated the pivotal role played by CD44 in the regulation of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. In the current study, we determined whether these effects resulted from an alteration in gut microbiota and the short-chain fatty acid (SCFA) production in CD44KO mice. Fecal transfer from naïve CD44KO but not CD44WT mice, into EAE-induced CD44WT mice, led to significant amelioration of EAE...
May 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28534275/sex-bias-in-pathogenesis-of-autoimmune-neuroinflammation-relevance-for-dimethyl-fumarate-immunomodulatory-anti-oxidant-action
#2
Zorica Stojić-Vukanić, Jelena Kotur-Stevuljević, Mirjana Nacka-Aleksić, Duško Kosec, Ivana Vujnović, Ivan Pilipović, Mirjana Dimitrijević, Gordana Leposavić
In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-γ+GM-CSF+IL-17+ subset...
May 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28533781/myelin-oligodendrocyte-glycoprotein-deciphering-a-target-in-inflammatory-demyelinating-diseases
#3
REVIEW
Patrick Peschl, Monika Bradl, Romana Höftberger, Thomas Berger, Markus Reindl
Myelin oligodendrocyte glycoprotein (MOG), a member of the immunoglobulin (Ig) superfamily, is a myelin protein solely expressed at the outermost surface of myelin sheaths and oligodendrocyte membranes. This makes MOG a potential target of cellular and humoral immune responses in inflammatory demyelinating diseases. Due to its late postnatal developmental expression, MOG is an important marker for oligodendrocyte maturation. Discovered about 30 years ago, it is one of the best-studied autoantigens for experimental autoimmune models for multiple sclerosis (MS)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28533380/ccr8-foxp3-treg-cells-as-master-drivers-of-immune-regulation
#4
Yiftah Barsheshet, Gizi Wildbaum, Eran Levy, Alon Vitenshtein, Chika Akinseye, Jeremy Griggs, Sergio A Lira, Nathan Karin
The current study identifies CCR8(+) regulatory T cells (Treg cells) as drivers of immunosuppression. We show that in human peripheral blood cells, more than 30% of Treg up-regulate CCR8 following activation in the presence of CCL1. This interaction induces STAT3-dependent up-regulation of FOXp3, CD39, IL-10, and granzyme B, resulting in enhanced suppressive activity of these cells. Of the four human CCR8 ligands, CCL1 is unique in potentiating Treg cells. The relevance of these observations has been extended using an experimental model of multiple sclerosis [experimental autoimmune encephalomyelitis, (EAE)] and a stabilized version of mouse CCL1 (CCL1-Ig)...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533365/prediction-of-disease-activity-in-models-of-multiple-sclerosis-by-molecular-magnetic-resonance-imaging-of-p-selectin
#5
Antoine Philippe Fournier, Aurélien Quenault, Sara Martinez de Lizarrondo, Maxime Gauberti, Gilles Defer, Denis Vivien, Fabian Docagne, Richard Macrez
New strategies for detecting disease activity in multiple sclerosis are being investigated to ameliorate diagnosis and follow-up of patients. Today, although magnetic resonance imaging (MRI) is widely used to diagnose and monitor multiple sclerosis, no imaging tools exist to predict the evolution of disease and the efficacy of therapeutic strategies. Here, we show that molecular MRI targeting the endothelial adhesion molecule P-selectin unmasks the pathological events that take place in the spinal cord of mice subjected to chronic or relapsing experimental autoimmune encephalomyelitis...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28522962/alterations-in-cd200-cd200r1-system-during-eae-already-manifest-at-presymptomatic-stages
#6
Tony Valente, Joan Serratosa, Unai Perpiñá, Josep Saura, Carme Solà
In the brain of patients with multiple sclerosis, activated microglia/macrophages appear in active lesions and in normal appearing white matter. However, whether they play a beneficial or a detrimental role in the development of the pathology remains a controversial issue. The production of pro-inflammatory molecules by chronically activated microglial cells is suggested to contribute to the progression of neurodegenerative processes in neurological disease. In the healthy brain, neurons control glial activation through several inhibitory mechanisms, such as the CD200-CD200R1 interaction...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28515278/critical-role-of-p2y12-receptor-in-regulation-of-th17-differentiation-and-experimental-autoimmune-encephalomyelitis-pathogenesis
#7
Chaoyan Qin, Jinfeng Zhou, Yuan Gao, Weiming Lai, Cuixia Yang, Yingying Cai, Shuai Chen, Changsheng Du
Adenosine 5'-diphosphate is a key endogenous cell-signaling molecule that can activate P2 purinergic receptor family members. ADP-P2Y signaling is reported to be associated with inflammation, but its function in T cell differentiation and autoimmune diseases pathogenesis is unclear. In this study, we found that the P2Y12 receptor was upregulated in the peripheral immune tissues of experimental autoimmune encephalomyelitis (EAE) mice. Deficiency of P2Y12 led to a reduced peak severity and cumulative disease score in EAE mice, followed by a dramatic reduction of leukocyte infiltration and less extensive demyelination...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28511127/neurophysiology-of-synaptic-functioning-in-multiple-sclerosis
#8
REVIEW
Mario Stampanoni Bassi, Francesco Mori, Fabio Buttari, Girolama A Marfia, Andrea Sancesario, Diego Centonze, Ennio Iezzi
Multiple sclerosis (MS) is an inflammatory immune-mediate disorder of the central nervous system (CNS), primarily affecting the myelin sheath and followed by neurodegeneration. Synaptic alterations are emerging as critical determinants of early neurodegeneration in MS. Inflammation-induced alterations of synaptic transmission and plasticity have been investigated in vitro and also in human MS using transcranial magnetic stimulation (TMS) techniques. Specific inflammatory cytokines alter glutamatergic and GABAergic transmission, resulting in synaptic hyperexcitability...
April 24, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/28507026/lineage-specific-metabolic-properties-and-vulnerabilities-of-t-cells-in-the-demyelinating-central-nervous-system
#9
Scott M Seki, Max Stevenson, Abagail M Rosen, Sanja Arandjelovic, Lelisa Gemta, Timothy N J Bullock, Alban Gaultier
Multiple sclerosis (MS) is a disease that is characterized by immune-mediated destruction of CNS myelin. Current MS therapies aim to block peripheral immune cells from entering the CNS. Although these treatments limit new inflammatory activity in the CNS, no treatment effectively prevents long-term disease progression and disability accumulation in MS patients. One explanation for this paradox is that current therapies are ineffective at targeting immune responses already present in the CNS. To this end, we sought to understand the metabolic properties of T cells that mediate ongoing inflammation in the demyelinating CNS...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28505283/oxidative-injury-and-iron-redistribution-are-pathological-hallmarks-of-marmoset-experimental-autoimmune-encephalomyelitis
#10
Jordon Dunham, Jan Bauer, Graham R Campbell, Don J Mahad, Nikki van Driel, Susanne M A van der Pol, Bert A 't Hart, Hans Lassmann, Jon D Laman, Jack van Horssen, Yolanda S Kap
Oxidative damage and iron redistribution are associated with the pathogenesis and progression of multiple sclerosis (MS), but these aspects are not entirely replicated in rodent experimental autoimmune encephalomyelitis (EAE) models. Here, we report that oxidative burst and injury as well as redistribution of iron are hallmarks of the MS-like pathology in the EAE model in the common marmoset. Active lesions in the marmoset EAE brain display increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox, and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions with active inflammation and demyelination, coinciding with enhanced expression of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2...
June 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28499934/matrine-promotes-oligodendrocyte-development-in-cns-autoimmunity-through-the-pi3k-akt-signaling-pathway
#11
Shuqing Liu, Mingliang Zhang, Huijun Zhang, Fangzhou Liu, Raojuan Chu, Guang-Xian Zhang, Lin Zhu
AIMS: Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, has been recently found to be beneficial in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mainly through its anti-inflammatory effect. In the present study, we tested the effect of MAT on ongoing EAE and defined possible mechanisms underlying its effects on myelination and oligodendrocytes. MAIN METHODS: EAE was induced in C57BL/6 mice and MAT treatment was started at disease onset...
May 9, 2017: Life Sciences
https://www.readbyqxmd.com/read/28495132/predicting-the-effects-of-potentially-therapeutic-modified-peptides-on-polyclonal-t-cell-populations-in-a-mouse-model-of-multiple-sclerosis
#12
Evan L Sauer, Elisabeth Trifilieff, Judith M Greer
Altered peptide ligands (APLs) have routinely been studied in clonal populations of Th cells that express a single T cell receptor (TCR), but results generated in this manner poorly predict the effects of APLs on polyclonal Th cells in vivo, contributing to the failure of phase II clinical trials of APLs in autoimmune diseases such as multiple sclerosis (MS). We have used a panel of APLs derived from an encephalitogenic epitope of myelin proteolipid protein to investigate the relationship between antigen cross-reactivity in a polyclonal environment, encephalitogenicity, and the capacity of an APL to provide protection against experimental autoimmune encephalomyelitis (EAE) in SJL mice...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28494768/inhibition-of-cd40-traf6-interactions-by-the-small-molecule-inhibitor-6877002-reduces-neuroinflammation
#13
Suzanne A B M Aarts, Tom T P Seijkens, Pascal J H Kusters, Susanne M A van der Pol, Barbara Zarzycka, Priscilla D A M Heijnen, Linda Beckers, Myrthe den Toom, Marion J J Gijbels, Louis Boon, Christian Weber, Helga E de Vries, Gerry A F Nicolaes, Christine D Dijkstra, Gijs Kooij, Esther Lutgens
BACKGROUND: The influx of leukocytes into the central nervous system (CNS) is a key hallmark of the chronic neuro-inflammatory disease multiple sclerosis (MS). Strategies that aim to inhibit leukocyte migration across the blood-brain barrier (BBB) are therefore regarded as promising therapeutic approaches to combat MS. As the CD40L-CD40 dyad signals via TNF receptor-associated factor 6 (TRAF6) in myeloid cells to induce inflammation and leukocyte trafficking, we explored the hypothesis that specific inhibition of CD40-TRAF6 interactions can ameliorate neuro-inflammation...
May 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28486971/a-role-for-cathepsin-z-in-neuroinflammation-provides-mechanistic-support-for-an-epigenetic-risk-factor-in-multiple-sclerosis
#14
Euan R O Allan, Rhiannon I Campden, Benjamin W Ewanchuk, Pankaj Tailor, Dale R Balce, Neil T McKenna, Catherine J Greene, Amy L Warren, Thomas Reinheckel, Robin M Yates
BACKGROUND: Hypomethylation of the cathepsin Z locus has been proposed as an epigenetic risk factor for multiple sclerosis (MS). Cathepsin Z is a unique lysosomal cysteine cathepsin expressed primarily by antigen presenting cells. While cathepsin Z expression has been associated with neuroinflammatory disorders, a role for cathepsin Z in mediating neuroinflammation has not been previously established. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in both wildtype mice and mice deficient in cathepsin Z...
May 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28479234/controlled-delivery-of-single-or-multiple-antigens-in-tolerogenic-nanoparticles-using-peptide-polymer-bioconjugates
#15
Ryan M Pearson, Liam M Casey, Kevin R Hughes, Leon Z Wang, Madeleine G North, Daniel R Getts, Stephen D Miller, Lonnie D Shea
Polymeric nanoparticles (NPs) have demonstrated their potential to induce antigen (Ag)-specific immunological tolerance in multiple immune models and are at various stages of commercial development. Association of Ag with NPs is typically achieved through surface coupling or encapsulation methods. However, these methods have limitations that include high polydispersity, uncontrollable Ag loading and release, and possible immunogenicity. Here, using antigenic peptides conjugated to poly(lactide-co-glycolide), we developed Ag-polymer conjugate NPs (acNPs) with modular loading of single or multiple Ags, negligible burst release, and minimally exposed surface Ag...
May 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28477198/characterization-of-th9-cells-in-the-development-of-eae-and-ibd
#16
Sakshi Malik, Valerie Dardalhon, Amit Awasthi
Encephalitogenic and colitogenic effector T cells have been implicated in the induction of experimental autoimmune encephalomyelitis (EAE) and inflammatory bowel disease (IBD), respectively. Effector functions of Th1 and Th17 cells have been well characterized and described for the induction and development of EAE and IBD; however, the recently identified Th9 cells have also been suggested to play an important role in these autoimmune pathologies. Th9 cells, primarily characterized by their high level of production of IL-9, are not only essential in controlling extracellular pathogens but also contribute to the development of autoimmunity and allergic inflammation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28474886/multivalent-soluble-antigen-arrays-exhibit-high-avidity-binding-and-modulation-of-b-cell-receptor-mediated-signaling-to-drive-efficacy-against-experimental-autoimmune-encephalomyelitis
#17
Brittany L Hartwell, Chad J Pickens, Martin Leon, Cory Berkland
A pressing need exists for antigen-specific immunotherapies (ASIT) that induce selective tolerance in autoimmune disease while avoiding deleterious global immunosuppression. Multivalent soluble antigen arrays (SAgAPLP:LABL), consisting of a hyaluronic acid (HA) linear polymer backbone cografted with multiple copies of autoantigen (PLP) and cell adhesion inhibitor (LABL) peptides, are designed to induce tolerance to a specific multiple sclerosis (MS) autoantigen. Previous studies established that hydrolyzable SAgAPLP:LABL, employing a degradable linker to codeliver PLP and LABL, was therapeutic in experimental autoimmune encephalomyelitis (EAE) in vivo and exhibited antigen-specific binding with B cells, targeted the B cell receptor (BCR), and dampened BCR-mediated signaling in vitro...
May 17, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28474276/sphingosine-toxicity-in-eae-and-ms-evidence-for-ceramide-generation-via-serine-palmitoyltransferase-activation
#18
Lawrence G Miller, Jennifer A Young, Swapan K Ray, Guanghu Wang, Sharad Purohit, Naren L Banik, Somsankar Dasgupta
Multiple sclerosis (MS) is a demyelinating disorder characterized by massive neurodegeneration and profound axonal loss. Since myelin is enriched with sphingolipids and some of them display toxicity, biological function of sphingolipids in demyelination has been investigated in MS brain tissues. An elevation of sphingosine with a decrease in monoglycosylceramide and psychosine (myelin markers) was observed in MS white matter and plaque compared to normal brain tissue. This indicated that sphingosine toxicity might mediate oligodendrocyte degeneration...
May 5, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28468969/protein-kinase-ck2-controls-the-fate-between-th17-cell-and-regulatory-t-cell-differentiation
#19
Sara A Gibson, Wei Yang, Zhaoqi Yan, Yudong Liu, Amber L Rowse, Amy S Weinmann, Hongwei Qin, Etty N Benveniste
CK2 is a highly conserved and pleiotropic serine/threonine kinase that promotes many prosurvival and proinflammatory signaling pathways, including PI3K/Akt/mTOR and JAK/STAT. These pathways are essential for CD4(+) T cell activation and polarization, but little is known about how CK2 functions in T cells. In this article, we demonstrate that CK2 expression and kinase activity are induced upon CD4(+) T cell activation. Targeting the catalytic activity of CK2 using the next-generation small molecule inhibitor CX-4945 in vitro significantly and specifically inhibited mouse and human Th17 cell differentiation while promoting the generation of Foxp3(+) regulatory T cells (Tregs)...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28467798/mechanism-of-oxidative-stress-p38mapk-sgk1-signaling-axis-in-experimental-autoimmune-encephalomyelitis-eae
#20
Liang Wang, Bin Li, Mo-Yuan Quan, Lin Li, Yuan Chen, Guo-Jun Tan, Jing Zhang, Xiao-Peng Liu, Li Guo
BACKGROUND: Multiple sclerosis (MS), a complex disease associated with multifocal demyelination of the central nervous system and poorly understood etiology. It has been previously indicated that many factors, including oxidative stress and p38MAPK-SGK1 pathway, contribute to the pathogenesis of MS. METHODS: This study, using an experimental autoimmune encephalomyelitis (EAE) model system, was aimed at investigating the molecular mechanisms determining interaction p38MAPK-SGK1 pathway and oxidative stress in MS pathogenesis...
April 12, 2017: Oncotarget
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