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Encephalomyelitis

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https://www.readbyqxmd.com/read/28209777/cd6-as-a-potential-target-for-treating-multiple-sclerosis
#1
Yan Li, Nora G Singer, Joy Whitbred, Michael A Bowen, David A Fox, Feng Lin
CD6 was established as a marker of T cells more than three decades ago, and recent studies have identified CD6 as a risk gene for multiple sclerosis (MS), a disease in which autoreactive T cells are integrally involved. Nevertheless, the precise role of CD6 in regulating T-cell responses is controversial and its significance in the pathogenesis of various diseases remains elusive, partly due to the lack of animals engineered to alter expression of the CD6 gene. In this report, we found that CD6 KO mice showed decreased pathogenic T-cell responses, reduced spinal cord T-cell infiltration, and attenuated disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
February 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28202908/silencing-c-rel-in-macrophages-dampens-th1-and-th17-immune-responses-and-alleviates-experimental-autoimmune-encephalomyelitis-in-mice
#2
Hongling Zhang, Jiacheng Bi, Huqiang Yi, Tingting Fan, Qingguo Ruan, Lintao Cai, Youhai H Chen, Xiaochun Wan
Autoimmune Th1 and Th17 responses are critical for the development of central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Although macrophages play important roles in the development of Th1 and Th17 responses, whether modulating macrophage gene transcription can diminish Th1- and Th17 cell-induced CNS pathology is unclear. In this study, we successfully silenced the expression of the transcription factor c-Rel in macrophages of mice with EAE (including those infiltrating the CNS) using chemically modified c-Rel-specific siRNAs delivered by nanoparticles...
February 16, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28199852/b-cell-activating-factor-baff-selects-il-10-b-cells-over-il-10-b-cells-during-inflammatory-responses
#3
Ning Ma, Yu Zhang, Qilin Liu, Zhiding Wang, Xiaoling Liu, Gaizhi Zhu, Dandan Yu, Gencheng Han, Guojiang Chen, Chunmei Hou, Tianxiao Wang, Yuanfang Ma, Beifen Shen, Yan Li, He Xiao, Renxi Wang
B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10(-)B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10(+) Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10(+)B cells over IL-10(-)B cells under noninflammatory conditions in vitro, whereas it expanded IL-10(-)B cells over IL-10(+)B cells during inflammatory responses, such as stimulation with autoantigen and LPS...
February 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28199198/the-immunological-function-of-gabaergic-system
#4
Chenlu Wu, Xiaobin Qin, Huihui Du, Nengzhang Li, Wenkai Ren, Yuanyi Peng
As a well-known inhibitory neurotransmitter in the central nervous system, gamma-aminobutyric acid also has critical roles in immune system. Immune cells (e.g., lymphocytes, macrophages) express the components of GABAergic system, including GABA receptors, GABA transporters, and GABA metabolic enzymes. The functions of immune cells are highly impacted on GABA signaling. GABAergic components negatively regulate the immune responses, particularly the T cell-mediated immunity, via their effects on production of pro-inflammatory cytokines and activation of signal pathways, like mitogen-activated protein kinase and nuclear factor-kappaB pathways...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28198408/therapeutic-effects-of-human-adipose-tissue-derived-stem-cell-hadsc-transplantation-on-experimental-autoimmune-encephalomyelitis-eae-mice
#5
Jia Li, Ying Chen, Zhibo Chen, Yuanyuan Huang, Dehao Yang, Zhongqian Su, Yiyun Weng, Xiang Li, Xu Zhang
This study is to investigate the therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) in mice. EAE mouse model was established by MOG35-55 immunization. Body weight and neurological function were assessed. H&E and LFB staining was performed to evaluate histopathological changes. Flow cytometry was used to detect Th17 and Treg cells. ELISA and real-time PCR were performed to determine transcription factor and pro-inflammatory cytokine levels...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196893/phosphorylation-of-%C3%AE-b-crystallin-supports-reactive-astrogliosis-in-demyelination
#6
Hedwich F Kuipers, Jane Yoon, Jack van Horssen, May H Han, Paul L Bollyky, Theo D Palmer, Lawrence Steinman
The small heat shock protein αB-crystallin (CRYAB) has been implicated in multiple sclerosis (MS) pathogenesis. Earlier studies have indicated that CRYAB inhibits inflammation and attenuates clinical disease when administered in the experimental autoimmune encephalomyelitis model of MS. In this study, we evaluated the role of CRYAB in primary demyelinating events. Using the cuprizone model of demyelination, a noninflammatory model that allows the analysis of glial responses in MS, we show that endogenous CRYAB expression is associated with increased severity of demyelination...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28196884/functional-genomics-analysis-of-vitamin-d-effects-on-cd4-t-cells-in-vivo-in-experimental-autoimmune-encephalomyelitis-%C3%A2
#7
Manuel Zeitelhofer, Milena Z Adzemovic, David Gomez-Cabrero, Petra Bergman, Sonja Hochmeister, Marie N'diaye, Atul Paulson, Sabrina Ruhrmann, Malin Almgren, Jesper N Tegnér, Tomas J Ekström, André Ortlieb Guerreiro-Cacais, Maja Jagodic
Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28194064/therapeutic-plasma-exchange-in-patients-with-neurologic-disorders-review-of-63-cases
#8
Anil Tombak, Mehmet Ali Uçar, Aydan Akdeniz, Arda Yilmaz, Hakan Kaleagası, Mehmet Ali Sungur, Eyup Naci Tiftik
Therapeutic plasma exchange (TPE) is a procedure that reduces circulating autoantibodies of the patients. TPE is commonly used in neurological disorders where autoimmunity plays a major role. We report our experience with regard to the indications, adverse events and outcomes of plasma exchange in neurological disorders. Sixty-three patients were included to this retrospective study. Median age was 48 years (range 1-85), there was a predominance of males. Neurological indications included Guillain-Barrè syndrome (n = 22), myasthenia gravis (n = 21), chronic inflammatory demyelinating polyneuropathy (n = 7), polymyositis (n = 3), multifocal motor neuropathy (n = 2), acute disseminated encephalomyelitis (n = 2), neuromyelitis optica (n = 2), multiple sclerosis (n = 2), limbic encephalitis (n = 1) and transverse myelitis (n = 1)...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28192476/th40-cells-cd4-cd40-tcells-drive-a-more-severe-form-of-experimental-autoimmune-encephalomyelitis-than-conventional-cd4-t-cells
#9
Gisela M Vaitaitis, Martin G Yussman, Dan M Waid, David H Wagner
CD40-CD154 interaction is critically involved in autoimmune diseases, and CD4 T cells play a dominant role in the Experimental Autoimmune Encephalomyelitis (EAE) model of Multiple Sclerosis (MS). CD4 T cells expressing CD40 (Th40) are pathogenic in type I diabetes but have not been evaluated in EAE. We demonstrate here that Th40 cells drive a rapid, more severe EAE disease course than conventional CD4 T cells. Adoptively transferred Th40 cells are present in lesions in the CNS and are associated with wide spread demyelination...
2017: PloS One
https://www.readbyqxmd.com/read/28191668/inflammatory-demyelination-induces-ependymal-modifications-concomitant-to-activation-of-adult-svz-stem-cell-proliferation
#10
Fereshteh Pourabdolhossein, Sara Gil-Perotín, Paula Garcia-Belda, Aurelien Dauphin, Sabah Mozafari, Vanja Tepavcevic, Jose Manuel Garcia Verdugo, Anne Baron-Van Evercooren
Ependymal cells (E1/E2) and ciliated B1cells confer a unique pinwheel architecture to the ventricular surface of the subventricular zone (SVZ), and their cilia act as sensors to ventricular changes during development and aging. While several studies showed that forebrain demyelination reactivates the SVZ triggering proliferation, ectopic migration, and oligodendrogenesis for myelin repair, the potential role of ciliated cells in this process was not investigated. Using conventional and lateral wall whole mount preparation immunohistochemistry in addition to electron microscopy in a forebrain-targeted model of experimental autoimmune encephalomyelitis (tEAE), we show an early decrease in numbers of pinwheels, B1 cells, and E2 cells...
February 13, 2017: Glia
https://www.readbyqxmd.com/read/28188174/brain-atrophy-in-picornavirus-infected-fvb-mice-is-dependent-on-the-h-2d-b-class-i-molecule
#11
April M Huseby Kelcher, Pascal A Atanga, Jeffrey D Gamez, Luz M Cumba Garcia, Stephanie J Teclaw, Kevin D Pavelko, Slobodan I Macura, Aaron J Johnson
Brain atrophy is a common feature of numerous neurologic diseases in which the role of neuroinflammation remains ill-defined. In this study, we evaluated the contribution of major histocompatibility complex class I molecules to brain atrophy in Theiler's murine encephalomyelitis virus (TMEV)-infected transgenic FVB mice that express the D(b) class I molecule. FVB/D(b) and wild-type FVB mice were evaluated for changes in neuroinflammation, virus clearance, neuropathology, and development of brain atrophy via T2-weighted MRI and subsequent 3-dimensional volumetric analysis...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28186117/amelioration-of-experimental-autoimmune-encephalomyelitis-through-transplantation-of-placental-derived-mesenchymal-stem-cells
#12
Hong Jiang, Yuanyuan Zhang, Kewei Tian, Beibei Wang, Shu Han
Placental derived mesenchymal stem cells (PMSCs) have been suggested as a possible source of cells to treat multiple sclerosis (MS) due to their immunomodulatory functions, lack of ethical concerns, and potential to differentiate into neurons and oligodendrocytes. To investigate whether PMSCs share similar characteristics with embryonic mesenchymal stem cells (EMSCs), and if transplanted PMSCs have the ability to integrate and replace degenerated neural cells, we transplanted rat PMSCs and EMSCs into the central nervous system (CNS) of Lewis rats with experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181561/peripheral-sensory-neuron-injury-contributes-to-neuropathic-pain-in-experimental-autoimmune-encephalomyelitis
#13
I-Ching Wang, Chen-Yen Chung, Fang Liao, Chih-Cheng Chen, Cheng-Han Lee
Multiple sclerosis (MS)-induced neuropathic pain deteriorates quality of life in patients but is often refractory to treatment. In experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, animals develop neuropathy and inflammation-induced tissue acidosis, which suggests the involvement of acid-sensing ion channels (ASICs). Also, peripheral neuropathy is reported in MS patients. However, the involvement of the peripheral nervous system (PNS) in MS neuropathic pain remains elusive. This study investigated the contribution of ASICs and peripheral neuropathy in MS-induced neuropathic pain...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174073/development-and-validation-of-sensitive-real-time-rt-pcr-assay-for-broad-detection-of-rabies-virus
#14
Martin Faye, Laurent Dacheux, Manfred Weidmann, Sylvie Audrey Diop, Cheikh Loucoubar, Hervé Bourhy, Amadou Alpha Sall, Ousmane Faye
Rabies virus (RABV) remains one of the most important global zoonotic pathogens. RABV causes rabies, an acute encephalomyelitis associated with a high rate of mortality in humans and animals and affecting different parts of the world, particularly in Asia and Africa. Confirmation of rabies diagnosis relies on laboratory diagnosis, in which molecular techniques such as detection of viral RNA by reverse transcription polymerase chain reaction (RT-PCR) are increasingly being used. In this study, two real-time quantitative RT-PCR assays were developed for large-spectrum detection of RABV, with a focus on African isolates...
February 4, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28173990/acute-disseminated-encephalomyelitis-a-gray-distinction
#15
Amal Abu Libdeh, Howard P Goodkin, Denia Ramirez-Montealegre, J Nicholas Brenton
BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an immune-mediated, inflammatory acquired demyelinating syndrome predominantly affecting the white matter of the central nervous system. METHODS: We describe a three-year-old boy whose clinical presentation was suspicious for ADEM but whose initial imaging abnormalities were confined to the deep gray matter (without evidence of white matter involvement). His clinical course was fluctuating and repeat imaging one week after presentation demonstrated interval development of characteristic white matter lesions...
January 12, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28168214/cerebrospinal-fluid-protein-carbonylation-identifies-oxidative-damage-in-autoimmune-demyelination
#16
David N Irani
Oxidative damage occurs in multiple sclerosis, but is difficult to identify antemortem and remains an unknown contributor to disease progression. Carbonylation is a quantitative measure of protein oxidation. Cerebrospinal fluid samples from multiple sclerosis patients showed elevated carbonylated protein levels compared to controls. In experimental autoimmune encephalomyelitis, carbonylated protein levels in cerebrospinal fluid correlated tightly with those found in inflamed spinal cord tissues. Furthermore, concentrations in cerebrospinal fluid and spinal cord responded in parallel to an antioxidant intervention that also attenuated disease symptoms...
February 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28167776/tgf-%C3%AE-inhibitor-smad7-regulates-dendritic-cell-induced-autoimmunity
#17
Dominika Lukas, Nir Yogev, Junda M Kel, Tommy Regen, Ilgiz A Mufazalov, Yilang Tang, Florian Wanke, Boris Reizis, Werner Müller, Florian C Kurschus, Marco Prinz, Ingo Kleiter, Björn E Clausen, Ari Waisman
TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28167760/sphingosine-1-phosphate-receptor-modulation-suppresses-pathogenic-astrocyte-activation-and-chronic-progressive-cns-inflammation
#18
Veit Rothhammer, Jessica E Kenison, Emily Tjon, Maisa C Takenaka, Kalil Alves de Lima, Davis M Borucki, Chun-Cheih Chao, Annabel Wilz, Manon Blain, Luke Healy, Jack Antel, Francisco J Quintana
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the CNS that causes disability in young adults as a result of the irreversible accumulation of neurological deficits. Although there are potent disease-modifying agents for its initial relapsing-remitting phase, these therapies show limited efficacy in secondary progressive MS (SPMS). Thus, there is an unmet clinical need for the identification of disease mechanisms and potential therapeutic approaches for SPMS. Here, we show that the sphingosine 1-phosphate receptor (S1PR) modulator fingolimod (FTY720) ameliorated chronic progressive experimental autoimmune encephalomyelitis in nonobese diabetic mice, an experimental model that resembles several aspects of SPMS, including neurodegeneration and disease progression driven by the innate immune response in the CNS...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28165507/paeoniflorin-ameliorates-experimental-autoimmune-encephalomyelitis-via-inhibition-of-dendritic-cell-function-and-th17-cell-differentiation
#19
Han Zhang, Yuanyuan Qi, Yuanyang Yuan, Li Cai, Haiyan Xu, Lili Zhang, Bing Su, Hong Nie
Paeoniflorin (PF) is a monoterpene glycoside and exhibits multiple effects, including anti-inflammation and immunoregulation. To date, the effect of PF on multiple sclerosis (MS) has not been investigated. In this study, we investigated the effect of PF in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. After administered with PF, the onset and clinical symptoms of EAE mice were significantly ameliorated, and the number of Th17 cells infiltrated in central nervous system (CNS) and spleen was also dramatically decreased...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28161558/neutrophil-perversion-in-demyelinating-autoimmune-diseases-mechanisms-to-medicine
#20
REVIEW
Courtney S Casserly, Julia C Nantes, Ryder F Whittaker Hawkins, Luc Vallières
Neutrophils are essential to a healthy life, yet pose a threat if improperly controlled. Neutrophil perversion is well documented in a variety of inflammatory disorders (e.g. arthritis, lupus, psoriasis), but is only beginning to be demystified in autoimmune demyelination, the most common cause of neurological disability in young adults. Using the animal model experimental autoimmune encephalomyelitis (EAE), several molecules that help neutrophils invade the central nervous system (CNS) have been identified...
February 2, 2017: Autoimmunity Reviews
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