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experimental autoimmune encephalomyelitis

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https://www.readbyqxmd.com/read/29150604/transcriptional-signature-of-human-pro-inflammatory-th17-cells-identifies-reduced-il10-gene-expression-in-multiple-sclerosis
#1
Dan Hu, Samuele Notarbartolo, Tom Croonenborghs, Bonny Patel, Ron Cialic, Tun-Hsiang Yang, Dominik Aschenbrenner, Karin M Andersson, Marco Gattorno, Minh Pham, Pia Kivisakk, Isabelle V Pierre, Youjin Lee, Karun Kiani, Maria Bokarewa, Emily Tjon, Nathalie Pochet, Federica Sallusto, Vijay K Kuchroo, Howard L Weiner
We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ(+)IL-17(+) (TH1/17) and IFN-γ(-)IL-17(+) (TH17) CD4(+) T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene signatures with marked similarity to mouse pathogenic TH17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that TH1/17 cells have elevated expression of CXCR3 and reduced expression of IFNG, CCL3, CLL4, GZMB, and IL10 compared to healthy controls...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29148731/conjugation-of-transforming-growth-factor-beta-to-antigen-loaded-poly-lactide-co-glycolide-nanoparticles-enhances-efficiency-of-antigen-specific-tolerance
#2
Liam M Casey, Ryan M Pearson, Kevin Hughes, Jeffrey Liu, Justin Rose, Madeleine G North, Leon Wang, Lei Mei, Stephen D Miller, Lonnie D Shea
Current strategies for treating autoimmunity involve the administration of broad-acting immunosuppressive agents that impair healthy immunity. Intravenous (i.v.) administration of poly(lactide-co-glycolide) nanoparticles (NPs) containing disease-relevant antigens (Ag-NPs) have demonstrated antigen(Ag)-specific immune tolerance in models of autoimmunity. However, subcutaneous (s.c.) delivery of Ag-NPs has not been effective. This investigation tested the hypothesis that co-delivery of the immunomodulatory cytokine, transforming growth factor beta 1 (TGF-β), on Ag-NPs would modulate the immune response to Ag-NPs and improve the efficiency of tolerance induction...
November 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29146590/camkii%C3%AE-mediates-the-effect-of-il-17-to-promote-ongoing-spontaneous-and-evoked-pain-in-multiple-sclerosis
#3
Xiaoyu Hu, Fang Huang, Zaijie Jim Wang
Pain is a common and severe symptom in multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the central nervous system. The neurobiological mechanism underlying MS pain is poorly understood. In this study, we investigated the role of Ca(2+)/calmodulin dependent kinase type IIα (CaMKIIα) in driving chronic pain in MS using a mouse experimental autoimmune encephalomyelitis (EAE) model. We found that spinal CaMKIIα activity was enhanced in EAE correlating with the development of ongoing spontaneous pain and evoked hypersensitivity to mechanical and thermal stimuli...
November 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29143823/salt-responsive-gut-commensal-modulates-th17-axis-and-disease
#4
Nicola Wilck, Mariana G Matus, Sean M Kearney, Scott W Olesen, Kristoffer Forslund, Hendrik Bartolomaeus, Stefanie Haase, Anja Mähler, András Balogh, Lajos Markó, Olga Vvedenskaya, Friedrich H Kleiner, Dmitry Tsvetkov, Lars Klug, Paul I Costea, Shinichi Sunagawa, Lisa Maier, Natalia Rakova, Valentin Schatz, Patrick Neubert, Christian Frätzer, Alexander Krannich, Maik Gollasch, Diana A Grohme, Beatriz F Côrte-Real, Roman G Gerlach, Marijana Basic, Athanasios Typas, Chuan Wu, Jens M Titze, Jonathan Jantsch, Michael Boschmann, Ralf Dechend, Markus Kleinewietfeld, Stefan Kempa, Peer Bork, Ralf A Linker, Eric J Alm, Dominik N Müller
A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (TH17) cells, which can also contribute to hypertension. Induction of TH17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus. Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating TH17 cells...
November 15, 2017: Nature
https://www.readbyqxmd.com/read/29141529/experimental-autoimmune-encephalomyelitis-eae-model-of-cynomolgus-macaques-induced-by-recombinant-human-mog1-125-rhmog1-125-protein-and-mog34-56-peptide
#5
Yunxiao Sun, Zhen Peng, Libiao Zhang, Huaqian Wang, Xiangyang He, Xingwen Peng, Qin Zhang, Hui Liu, Junhua Rao, Haifeng Wang, Jie Wu
Experimental autoimmune encephalomyelitis (EAE) induced by self-myelin antigen is a widely used multiple sclerosis (MS) model for preclinical studies of new therapeutics and potential pathogenesis. By comparison with rodent EAE models, EAE models in primates are more similar to MS. Some groups have developed EAE models in primates by using common marmoset (Callithrix jacchus). However, this model has some limitations. EAE in cynomolgus monkey (Macaque fasciculrais) could overcome these limitations. In this study, EAE was induced in cynomolgus monkey by immunizing with the recombinant human myelin oligodendrocyte glycoprotein extracellular domain (1-125) (rhMOG1-125) and a synthetic peptide, representing peptide 34-56 of human myelin oligodendrocyte glycoprotein (MOG34-56) in complete Freund's adjuvant (CFA) and in combination with intravenous injection of pertussis toxin, and subsequent booster immunizations with the same dose of antigen in incomplete Freund's adjuvant (IFA) until the animals developed clinically significant EAE (score≥2)...
November 9, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29140922/fingolimod-reduces-neuropathic-pain-behaviors-in-a-mouse-model-of-multiple-sclerosis-by-a-sphingosine-1-phosphate-receptor-1-dependent-inhibition-of-central-sensitization-in-the-dorsal-horn
#6
Suzanne Doolen, Tommaso Iannitti, Benjamin C Shaw, Carolyn M Grachen, Renee R Donahue, Bradley K Taylor
Multiple sclerosis (MS) is an autoimmune-inflammatory neurodegenerative disease that is often accompanied by a debilitating neuropathic pain. Disease-modifying agents slow the progression of MS and prevent relapses, yet it remains unclear if they yield analgesia. We explored the analgesic potential of fingolimod (FTY720), an agonist/functional antagonist at the sphingosine-1-phosphate receptor 1 (S1PR1), because it reduces hyperalgesia in models of peripheral inflammatory and neuropathic pain. We used a myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) mouse model of experimental autoimmune encephalomyelitis (EAE), modified to avoid frank paralysis and thus allow for assessment of withdrawal behaviors to somatosensory stimuli...
November 13, 2017: Pain
https://www.readbyqxmd.com/read/29136024/severe-oxidative-stress-in-an-acute-inflammatory-demyelinating-model-in-the-rhesus-monkey
#7
Jordon Dunham, Reinofke van de Vis, Jan Bauer, Jacqueline Wubben, Nikki van Driel, Jon D Laman, Bert A 't Hart, Yolanda S Kap
Oxidative stress is increasingly implicated as a co-factor of tissue injury in inflammatory/demyelinating disorders of the central nervous system (CNS), such as multiple sclerosis (MS). While rodent experimental autoimmune encephalomyelitis (EAE) models diverge from human demyelinating disorders with respect to limited oxidative injury, we observed that in a non-human primate (NHP) model for MS, namely EAE in the common marmoset, key pathological features of the disease were recapitulated, including oxidative tissue injury...
2017: PloS One
https://www.readbyqxmd.com/read/29132838/therapeutic-effects-of-diosgenin-in-experimental-autoimmune-encephalomyelitis
#8
Weili Liu, Mei Zhu, Zhongwang Yu, Dou Yin, Fengfeng Lu, Yingyan Pu, Chao Zhao, Cheng He, Li Cao
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system. Currently, there is no drug available to cure this kind of disease. Diosgenin is a plant-derived steroid saponin. A previous study in our lab revealed that diosgenin can promote oligodendrocyte progenitor cell differentiation and accelerate remyelination. In the present study, we found that diosgenin dose-dependently alleviated the progression of experimental autoimmune encephalomyelitis with reduced central nervous system inflammation and demyelination...
October 31, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29131010/blockade-of-experimental-multiple-sclerosis-by-inhibition-of-the-acid-sphingomyelinase-ceramide-system
#9
Katrin Anne Becker, Ramona Halmer, Laura Davies, Brian D Henry, Regan Ziobro-Henry, Yann Decker, Yang Liu, Erich Gulbins, Klaus Fassbender, Silke Walter
BACKGROUND: Multiple sclerosis (MS) is a severe and common autoimmune disorder of the central nervous system. Despite the availability of several novel treatment options, the disease is still poorly controlled, since the pathophysiological mechanisms are not fully understood. METHODS: We tested the role of the acid sphingomyelinase/ceramide system in a model of MS, i.e. experimental autoimmune encephalomyelitis (EAE). Mice were immunized with myelin-oligodendrocyte glycoprotein and the development of the disease was analyzed by histology, immunological tests and clinical assessment in wildtype and acid sphingomyelinase (Asm)-deficient mice...
November 6, 2017: Neuro-Signals
https://www.readbyqxmd.com/read/29128575/strain-specificities-in-age-related-changes-in-mechanisms-promoting-and-controlling-rat-spinal-cord-damage-in-experimental-autoimmune-encephalomyelitis
#10
Zorica Stojić-Vukanić, Ivan Pilipović, Jasmina Djikić, Ivana Vujnović, Mirjana Nacka-Aleksić, Biljana Bufan, Nevena Arsenović-Ranin, Duško Kosec, Gordana Leposavić
The study investigated strain specificities in age-related differences in CD8+ T cell- and microglial cell-mediated mechanisms implicated in induction/perpetuation and/or control of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in Albino Oxford (AO) and Dark Agouti (DA) rats exhibiting age-related changes in the susceptibility to EAE in the opposite direction (increase in relatively resistant AO rats vs decrease in DA rats). In the inductive phase of EAE, the greater number of fully differentiated effector CD8+ T lymphocytes was found in draining lymph nodes (dLNs) from aged rats of both strains than in strain-matched young rats, but this was particularly prominent in AO rats, which exhibited milder EAE of prolonged duration compared with their DA counterparts...
November 8, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29127843/ifn-%C3%AE-regulates-th17-differentiation-partly-through-the-inhibition-of-osteopontin-in-experimental-autoimmune-encephalomyelitis
#11
Qing Zhao, Wenjing Cheng, Yebin Xi, Zheyi Cao, Yunzhi Xu, Ting Wu, Chengzhen Li, Xiaoyin Niu, Guangjie Chen
Multiple sclerosis (MS) and the corresponding animal model, experimental autoimmune encephalomyelitis (EAE), are chronic neuroinflammatory autoimmune diseases. Increased activation of CD4+T cells, especially the Th1 and Th17 subsets, is thought to play a causal role in this disease. IFN-β is widely used in the treatment of MS and is found to decrease IL-17 and OPN production in MS patients and EAE mice. However, a definitive molecular mechanism has not yet been fully elucidated. In this study, we investigated the immunomodulatory effect of IFN-β on the EAE model...
November 7, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29123469/suppression-of-inflammatory-demyelinaton-and-axon-degeneration-through-inhibiting-kv3-channels
#12
Peter Jukkola, Yuanzheng Gu, Amy E Lovett-Racke, Chen Gu
The development of neuroprotective and repair strategies for treating progressive multiple sclerosis (MS) requires new insights into axonal injury. 4-aminopyridine (4-AP), a blocker of voltage-gated K(+) (Kv) channels, is used in symptomatic treatment of progressive MS, but the underlying mechanism remains unclear. Here we report that deleting Kv3.1-the channel with the highest 4-AP sensitivity-reduces clinical signs in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. In Kv3.1 knockout (KO) mice, EAE lesions in sensory and motor tracts of spinal cord were markedly reduced, and radial astroglia were activated with increased expression of brain derived neurotrophic factor (BDNF)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29121970/endothelial-%C3%AE-6%C3%AE-4-integrin-protects-during-experimental-autoimmune-encephalomyelitis-induced-neuroinflammation-by-maintaining-vascular-integrity-and-tight-junction-protein-expression
#13
Jennifer V Welser, Sebok K Halder, Ravi Kant, Amin Boroujerdi, Richard Milner
BACKGROUND: Extracellular matrix (ECM) proteins play critical functions regulating vascular formation and function. Laminin is a major component of the vascular basal lamina, and transgenic mice deficient in astrocyte or pericyte laminin show defective blood-brain barrier (BBB) integrity, indicating an important instructive role for laminin in cerebral blood vessels. As previous work shows that in the normal brain, vascular expression of the laminin receptor α6β4 integrin is predominantly restricted to arterioles, but induced on all vessels during neuroinflammation, it is important to define the role of this integrin in the maintenance of BBB integrity...
November 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29119385/intestinal-permeabiliy-in-relapsing-remitting-multiple-sclerosis
#14
REVIEW
M C Buscarinu, S Romano, R Mechelli, R Pizzolato Umeton, M Ferraldeschi, A Fornasiero, R Reniè, B Cerasoli, E Morena, C Romano, N D Loizzo, R Umeton, M Salvetti, G Ristori
Changes of intestinal permeability (IP) have been extensively investigated in inflammatory bowel diseases (IBD) and celiac disease (CD), underpinned by a known unbalance between microbiota, IP and immune responses in the gut. Recently the influence of IP on brain function has greatly been appreciated. Previous works showed an increased IP that preceded experimental autoimmune encephalomyelitis development and worsened during disease with disruption of TJ. Moreover, studying co-morbidity between Crohn's disease and MS, a report described increased IP in a minority of cases with MS...
November 8, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29114087/the-cooling-compound-icilin-attenuates-autoimmune-neuroinflammation-through-modulation-of-the-t-cell-response
#15
Benjamin W Ewanchuk, Euan R O Allan, Amy L Warren, Rithwik Ramachandran, Robin M Yates
The synthetic supercooling drug, icilin, and its primary receptor target, the cation channel transient receptor potential (TRP) melastatin-8 (TRPM8), have been described as potent negative regulators of inflammation in the colon. The aim of this study was to determine whether the anti-inflammatory action of icilin could potentially be used to treat autoimmune neuroinflammatory disorders, such as multiple sclerosis (MS). During experimental autoimmune encephalomyelitis (EAE)-a CD4(+) T cell-driven murine model of MS-we found that both wild-type (WT) and TRPM8-deficient EAE mice were protected from disease progression during icilin treatment, as evidenced by delays in clinical onset and reductions in neuroinflammation...
November 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29111742/increased-post-translational-lysine-acetylation-of-myelin-basic-protein-is-associated-with-peak-neurological-disability-in-a-mouse-experimental-autoimmune-encephalomyelitis-model-of-multiple-sclerosis
#16
Ryan Lillico, Ting Zhou, Tina Khorshid Ahmad, Nicholas Stesco, Kiana Gozda, Jessica Truong, Jiming Kong, Ted M Lakowski, Michael Namaka
Citrullination of arginine residues is a post-translational modification (PTM) found on myelin basic protein (MBP), which neutralizes MBPs positive charge, and is implicated in myelin damage and multiple sclerosis (MS). Here we identify lysine acetylation as another neutralizing PTM to MBP that may be involved in myelin damage. We quantify changes in lysine and arginine PTMs on MBP derived from mice induced with an experimental autoimmune encephalomyelitis (EAE) model of MS using liquid chromatography tandem mass spectrometry...
November 7, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29107957/febuxostat-ameliorates-secondary-progressive-experimental-autoimmune-encephalomyelitis-by-restoring-mitochondrial-energy-production-in-a-got2-dependent-manner
#17
Josephe A Honorat, Yuji Nakatsuji, Mikito Shimizu, Makoto Kinoshita, Hisae Sumi-Akamaru, Tsutomu Sasaki, Kazushiro Takata, Toru Koda, Akiko Namba, Kazuya Yamashita, Eri Sanda, Manabu Sakaguchi, Atsushi Kumanogoh, Takashi Shirakura, Mizuho Tamura, Saburo Sakoda, Hideki Mochizuki, Tatsusada Okuno
Oxidative stress and mitochondrial dysfunction are important determinants of neurodegeneration in secondary progressive multiple sclerosis (SPMS). We previously showed that febuxostat, a xanthine oxidase inhibitor, ameliorated both relapsing-remitting and secondary progressive experimental autoimmune encephalomyelitis (EAE) by preventing neurodegeneration in mice. In this study, we investigated how febuxostat protects neuron in secondary progressive EAE. A DNA microarray analysis revealed that febuxostat treatment increased the CNS expression of several mitochondria-related genes in EAE mice, most notably including GOT2, which encodes glutamate oxaloacetate transaminase 2 (GOT2)...
2017: PloS One
https://www.readbyqxmd.com/read/29101799/s-allyl-cysteine-improves-clinical-and-neuropathological-features-of-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice
#18
Hossein Zeinali, Tourandokht Baluchnejadmojarad, Soudabeh Fallah, Mohsen Sedighi, Nariman Moradi, Mehrdad Roghani
Multiple sclerosis (MS) is a deleterious autoimmune and demyelinating disorder of the central nervous system with debilitating sensory and motor complications. There is still no definite cure for it and the main focus for its treatment mostly pivots around subsiding its severity and recurrence. Experimental autoimmune encephalomyelitis (EAE) is an established animal model of MS. S-allyl cysteine (SAC) is the active and main constituent of aged garlic extract with anti-inflammatory and neuroprotective property...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29101111/the-interleukin-il-23-t-helper-th-17-axis-in-experimental-autoimmune-encephalomyelitis-and-multiple-sclerosis
#19
Michael Hiltensperger, Thomas Korn
T helper (Th)17 cells are responsible for host defense against fungi and certain extracellular bacteria but have also been reported to play a role in a variety of autoimmune diseases. Th17 cells respond to environmental cues, are very plastic, and might also be involved in tissue homeostasis and regeneration. The imprinting of pathogenic properties in Th17 cells in autoimmunity seems highly dependent on interleukin (IL)-23. Since Th17 cells were first described in experimental autoimmune encephalomyelitis, they have been suggested to also promote tissue damage in multiple sclerosis (MS)...
November 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29101043/the-influence-and-impact-of-ageing-and-immunosenescence-isc-on-adaptive-immunity-during-multiple-sclerosis-ms-and-the-animal-counterpart-experimental-autoimmune-encephalomyelitis-eae
#20
REVIEW
Christopher Bolton, Paul A Smith
The human ageing process encompass mechanisms that effect a decline in homeostasis with increased susceptibility to disease and the development of chronic life-threatening illness. Increasing age affects the immune system which undergoes a progressive loss of efficiency, termed immunosenescence (ISC), to impact on quantitative and functional aspects of innate and adaptive immunity. The human demyelinating disease multiple sclerosis (MS) and the corresponding animal model experimental autoimmune encephalomyelitis (EAE) are strongly governed by immunological events that primarily involve the adaptive arm of the immune response...
October 31, 2017: Ageing Research Reviews
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