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experimental autoimmune encephalomyelitis

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https://www.readbyqxmd.com/read/28344072/osteopontin-metallothionen-i-ii-interactions-in-experimental-autoimmunune-encephalomyelitis
#1
Hrvoje Jakovac, Tanja Grubić Kezele, Sandra Šućurović, Biserka Mulac-Jeričević, Biserka Radošević-Stašić
Osteopontin (OPN), an extracellular matrix (ECM) glyco-phosphoprotein, plays an important role in autoimmune-mediated demyelinating diseases, including multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). As an integrin and CD44 binding protein it participates in bidirectional communication between the ECM and target cells and affects transduction pathways that maintain neuronal and immune cells homeostasis. Its biological activity is also heavily influenced by microenvironment, which stimulates the cleavage of OPN and changes its functions...
March 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28341037/influenza-virus-infection-exacerbates-experimental-autoimmune-encephalomyelitis-disease-by-promoting-type-i-t-cells-infiltration-into-central-nervous-system
#2
Qingyun Chen, Yinping Liu, Aizhen Lu, Ke Ni, Zheng Xiang, Kun Wen, Wenwei Tu
Multiple sclerosis starts with increased migration of auto-reactive lymphocytes across the blood-brain barrier, resulting in persistent neurodegeneration. Clinical and epidemiological studies indicated upper respiratory viral infections are associated with clinical exacerbation of multiple sclerosis. However, so far there is no any direct evidence to support it. Using the experimental autoimmune encephalomyelitis mice as the model for multiple sclerosis, we demonstrated that mice experienced with influenza virus infection were unable to recover from experimental autoimmune encephalomyelitis with a long-term exacerbation...
February 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28338530/pharmacologic-characterizations-of-a-p2x7-receptor-specific-radioligand-11c-gsk1482160-for-neuroinflammatory-response
#3
Junbin Han, Hui Liu, Chunling Liu, Hongjun Jin, Joel S Perlmutter, Terrance M Egan, Zhude Tu
OBJECTIVE: The P2X7 receptor (P2X7R) is a key regulatory element in the neuroinflammatory cascade that provides a promising target for imaging neuroinflammation. GSK1482160, a P2X7R modulator with nanomolar binding affinity and high selectivity, has been successfully radiolabeled and utilized for imaging P2X7 levels in a mouse model of lipopolysaccharide-induced systemic inflammation. In the current study, we further characterized its binding profile and determined whether [C]GSK1482160 can detect changes in P2X7R expression in a rodent model of multiple sclerosis...
March 23, 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28336414/ccr6-th-cells-in-the-cerebrospinal-fluid-of-persons-with-multiple-sclerosis-are-dominated-by-pathogenic-non-classic-th1-cells-and-gm-csf-only-secreting-th-cells
#4
S M Restorick, L Durant, S Kalra, G Hassan-Smith, E Rathbone, M R Douglas, S J Curnow
Considerable attention has been given to CCR6(+) IL-17-secreting CD4(+) T cells (Th17) in the pathology of a number of autoimmune diseases including multiple sclerosis (MS). However, other Th subsets also play important pathogenic roles, including those that secrete IFNγ and GM-CSF. CCR6 expression by Th17 cells allows their migration across the choroid plexus into the cerebrospinal fluid (CSF), where they are involved in the early phase of experimental autoimmune encephalomyelitis (EAE), and in MS these cells are elevated in the CSF during relapses and contain high frequencies of autoreactive cells...
March 20, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28330904/autonomous-tnf-is-critical-for-in-vivo-monocyte-survival-in-steady-state-and-inflammation
#5
Yochai Wolf, Anat Shemer, Michal Polonsky, Mor Gross, Alexander Mildner, Simon Yona, Eyal David, Ki-Wook Kim, Tobias Goldmann, Ido Amit, Mathias Heikenwalder, Sergei Nedospasov, Marco Prinz, Nir Friedman, Steffen Jung
Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart...
March 22, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28321419/pvaxhsp65-vaccination-primes-for-high-il-10-production-and-decreases-experimental-encephalomyelitis-severity
#6
Sofia Fernanda Gonçalves Zorzella-Pezavento, Fernanda Chiuso-Minicucci, Thais Graziela Donegá França, Larissa Lumi Watanabe Ishikawa, Larissa Camargo da Rosa, Priscila Maria Colavite, Bianca Balbino, Camila Marques, Maura Rosane Valerio Ikoma, Ana Paula Masson, Célio Lopes Silva, Alexandrina Sartori
Experimental autoimmune encephalomyelitis (EAE) is a demyelinating pathology of the central nervous system (CNS) used as a model to study multiple sclerosis immunopathology. EAE has also been extensively employed to evaluate potentially therapeutic schemes. Considering the presence of an immune response directed to heat shock proteins (hsps) in autoimmune diseases and the immunoregulatory potential of these molecules, we evaluated the effect of a previous immunization with a genetic vaccine containing the mycobacterial hsp65 gene on EAE development...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28320969/ena-vasp-proteins-regulate-activated-t-cell-trafficking-by-promoting-diapedesis-during-transendothelial-migration
#7
Miriam L Estin, Scott B Thompson, Brianna Traxinger, Marlie H Fisher, Rachel S Friedman, Jordan Jacobelli
Vasodilator-stimulated phosphoprotein (VASP) and Ena-VASP-like (EVL) are cytoskeletal effector proteins implicated in regulating cell morphology, adhesion, and migration in various cell types. However, the role of these proteins in T-cell motility, adhesion, and in vivo trafficking remains poorly understood. This study identifies a specific role for EVL and VASP in T-cell diapedesis and trafficking. We demonstrate that EVL and VASP are selectively required for activated T-cell trafficking but are not required for normal T-cell development or for naïve T-cell trafficking to lymph nodes and spleen...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320131/epigenetic-and-gene-expression-alterations-of-foxp3-in-the-t-cells-of-eae-mouse-model-of-multiple-sclerosis
#8
Ali Noori-Zadeh, Seyed Alireza Mesbah-Namin, Ali Akbar Saboor-Yaraghi
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28315956/axonal-transport-deficits-in-multiple-sclerosis-spiraling-into-the-abyss
#9
REVIEW
Robert van den Berg, Casper C Hoogenraad, Rogier Q Hintzen
The transport of mitochondria and other cellular components along the axonal microtubule cytoskeleton plays an essential role in neuronal survival. Defects in this system have been linked to a large number of neurological disorders. In multiple sclerosis (MS) and associated models such as experimental autoimmune encephalomyelitis (EAE), alterations in axonal transport have been shown to exist before neurodegeneration occurs. Genome-wide association (GWA) studies have linked several motor proteins to MS susceptibility, while neuropathological studies have shown accumulations of proteins and organelles suggestive for transport deficits...
March 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28315676/the-major-histocompatibility-complex-class-iii-haplotype-ltab-ncr3-regulates-adjuvant-induced-but-not-antigen-induced-autoimmunity
#10
Anthony C Y Yau, Jonatan Tuncel, Rikard Holmdahl
Rheumatoid arthritis is a complex disease associated with >100 risk loci, with the strongest association from the major histocompatibility complex (MHC) region. Here, we analyzed a new genetic association in the MHC class-III region (MHC-III) using adjuvant- and antigen-induced arthritis models. In addition, we used models for multiple sclerosis for comparison and dissected the MHC-III-mediated mechanisms of importance for antibody and T-cell responses to antigens. With the use of a panel of MHC-III recombinant inbred strains, we found that the 33-kb Ltab-Ncr3 haplotype in MHC-III was linked to the induction of arthritis with incomplete Freund's adjuvant, with similar effects in arthritis induced by several oil adjuvants (hexadecane, heptadecane, squalene, arlacel)...
March 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28302146/relationship-of-acute-axonal-damage-wallerian-degeneration-and-clinical-disability-in-multiple-sclerosis
#11
Shailender Singh, Tobias Dallenga, Anne Winkler, Shanu Roemer, Brigitte Maruschak, Heike Siebert, Wolfgang Brück, Christine Stadelmann
BACKGROUND: Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. METHODS: Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions...
March 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28302135/myeloid-c-ebp%C3%AE-deficiency-reshapes-microglial-gene-expression-and-is-protective-in-experimental-autoimmune-encephalomyelitis
#12
Marta Pulido-Salgado, Jose M Vidal-Taboada, Gerardo Garcia Diaz-Barriga, Joan Serratosa, Tony Valente, Paola Castillo, Jonathan Matalonga, Marco Straccia, Josep M Canals, Annabel Valledor, Carme Solà, Josep Saura
BACKGROUND: CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage, but the involvement in this neuroprotective effect of the various C/EBPβ-expressing cell types is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture, we hypothesized that specific C/EBPβ deficiency in microglia could be neuroprotective in vivo...
March 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28302134/microrna-142-regulates-inflammation-and-t-cell-differentiation-in-an-animal-model-of-multiple-sclerosis
#13
Farideh Talebi, Samira Ghorbani, Wing Fuk Chan, Roobina Boghozian, Farimah Masoumi, Sedigheh Ghasemi, Mohammed Vojgani, Christopher Power, Farshid Noorbakhsh
BACKGROUND: MicroRNAs have emerged as an important class of modulators of gene expression. These molecules influence protein synthesis through translational repression or degradation of mRNA transcripts. Herein, we investigated the potential role of miR-142a isoforms, miR-142a-3p and miR-142a-5p, in the context of autoimmune neuroinflammation. METHODS: The expression levels of two mature isoforms of miR-142 were measured in the brains of patients with multiple sclerosis (MS) and the CNS tissues from mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
March 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28299403/effects-of-ifn-%C3%AE-1a-and-ifn-%C3%AE-1b-treatment-on-the-expression-of-cytokines-inducible-nos-nos-type-ii-and-myelin-proteins-in-animal-model-of-multiple-sclerosis
#14
Natalia Lubina-Dąbrowska, Adam Stepień, Grzegorz Sulkowski, Beata Dąbrowska-Bouta, Józef Langfort, Małgorzata Chalimoniuk
The aim of this study was to investigate the effects of interferon (IFN)-β1a and IFN-β1b treatment on inflammatory factors and myelin protein levels in the brain cortex of the Lewis rat experimental autoimmune encephalomyelitis (EAE), animal model of multiple sclerosis. To induce EAE, rat were immunized with inoculums containing spinal cord guinea pig homogenized in phosphate-buffered saline and emulsified in Freund's complete adjuvant containing 110 µg of the appropriate antigen in 100 µl of an emulsion and additionally 4-mg/ml Mycobacterium tuberculosis (H37Ra)...
March 15, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28292961/modeling-month-season-of-birth-as-a-risk-factor-in-mouse-models-of-chronic-disease-from-multiple-sclerosis-to-autoimmune-encephalomyelitis
#15
Jacob D Reynolds, Laure K Case, Dimitry N Krementsov, Abbas Raza, Rose Bartiss, Cory Teuscher
Month-season of birth (M-SOB) is a risk factor in multiple chronic diseases, including multiple sclerosis (MS), where the lowest and greatest risk of developing MS coincide with the lowest and highest birth rates, respectively. To determine whether M-SOB effects in such chronic diseases as MS can be experimentally modeled, we examined the effect of M-SOB on susceptibility of C57BL/6J mice to experimental autoimmune encephalomyelitis (EAE). As in MS, mice that were born during the M-SOB with the lowest birth rate were less susceptible to EAE than mice born during the M-SOB with the highest birth rate...
March 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28289417/murine-cytomegalovirus-infection-induces-susceptibility-to-eae-in-resistant-balb-c-mice
#16
Jelena Milovanovic, Branka Popovic, Marija Milovanovic, Daria Kvestak, Aleksandar Arsenijevic, Bojana Stojanovic, Irena Tanaskovic, Astrid Krmpotic, Nebojsa Arsenijevic, Stipan Jonjic, Miodrag L Lukic
In contrast to C57BL/6 mice, BALB/c mice are relatively resistant to the induction of experimental autoimmune encephalomyelitis (EAE) after challenge with MOG35-55 peptide. Here, we provide the first evidence that infection with murine cytomegalovirus (MCMV) in adulthood abrogates this resistance. Infected BALB/c mice developed clinical and histological signs similar to those seen in susceptible C57BL/6 mice. In addition to CD4(+) cells, large proportion of cells in the infiltrate of diseased BALB/c mice was CD8(+), similar with findings in multiple sclerosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28289410/autophagy-and-autophagy-related-proteins-in-cns-autoimmunity
#17
REVIEW
Christian W Keller, Jan D Lünemann
Autophagy comprises a heterogeneous group of cellular pathways that enables eukaryotic cells to deliver cytoplasmic constituents for lysosomal degradation, to recycle nutrients, and to survive during starvation. In addition to these primordial functions, autophagy has emerged as a key mechanism in orchestrating innate and adaptive immune responses and to shape CD4(+) T cell immunity through delivery of peptides to major histocompatibility complex (MHC) class II-containing compartments (MIICs). Individual autophagy proteins additionally modulate expression of MHC class I molecules for CD8(+) T cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28288184/cd73-is-expressed-by-inflammatory-th17-cells-in-experimental-autoimmune-encephalomyelitis-but-does-not-limit-differentiation-or-pathogenesis
#18
Gerard Hernandez-Mir, Mandy J McGeachy
CD73 works together with CD39 to convert extracellular ATP to immunoregulatory adenosine, thus inhibiting inflammation. TGFβ-mediated CD73 expression on 'regulatory' Th17 cells limits their ability to eradicate tumors, similar to the immunosuppressive mechanism described for CD73 on Tregs. However, CD73 is also expressed on Th17 cells thought to be inflammatory in Crohn's disease. CD73 has previously been reported to contribute to inflammation in the central nervous system (CNS). In experimental autoimmune encephalomyelitis (EAE), we found that inflammatory cytokine-producing Th17 cells showed increased CD73 expression as disease progressed...
2017: PloS One
https://www.readbyqxmd.com/read/28287595/bioluminescence-and-near-infrared-imaging-of-optic-neuritis-and-brain-inflammation-in-the-eae-model-of-multiple-sclerosis-in-mice
#19
Katja Schmitz, Irmgard Tegeder
Experimental autoimmune encephalomyelitis (EAE) in SJL/J mice is a model for relapsing-remitting multiple sclerosis (RRMS). Clinical EAE scores describing motor function deficits are basic readouts of the immune-mediated inflammation of the spinal cord. However, scores and body weight do not allow for an in vivo assessment of brain inflammation and optic neuritis. The latter is an early and frequent manifestation in about 2/3 of MS patients. Here, we show methods for bioluminescence and near-infrared live imaging to assess EAE evoked optic neuritis, brain inflammation, and blood-brain barrier (BBB) disruption in living mice using an in vivo imaging system...
March 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28284714/strain-specificities-in-cellular-and-molecular-immunopathogenic-mechanisms-underlying-development-of-experimental-autoimmune-encephalomyelitis-in-aged-rats
#20
Mirjana Nacka-Aleksić, Zorica Stojić-Vukanić, Ivan Pilipović, Ivana Vujnović, Biljana Bufan, Mirjana Dimitrijević, Gordana Leposavić
To understand strain-specificities of immune system in aged rats and their immunopathological implications, CD4+ T lymphocyte-mediated neuroinflammation in experimental autoimmune encephalomyelitis (EAE) was studied in two strains. Upon immunization for EAE, 22-24-month-old Albino Oxford (AO) rats developed milder neurological deficit of prolonged duration compared with their Dark Agouti (DA) counterparts. Consistently, they exhibited: (i) diminished neuroantigen-specific CD4+ T lymphocyte generation in draining lymph nodes (reflecting lower density of high-affinity IL-2 receptor complex on their surface and higher CD4+FoxP3+CD25+ regulatory cell frequency); (ii) less favorable spinal cord expression of CXCL12 and CCL2, and consequently diminished infiltration of neuroantigen-specific CD4+ T lymphocytes, including highly pathogenic IL-17+IFN-γ+ ones, and inflammatory monocytes into the spinal cord and (iii) subsequently impaired CD4+ T lymphocyte reactivation/survival and differentiation into highly pathogenic IL-17+ cells (reflecting downregulated expression of IL-1β, IL-6 and IL-23/p19)...
March 8, 2017: Mechanisms of Ageing and Development
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