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experimental autoimmune encephalomyelitis

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https://www.readbyqxmd.com/read/28087667/prmt5-selective-inhibitors-suppress-inflammatory-t-cell-responses-and-experimental-autoimmune-encephalomyelitis
#1
Lindsay M Webb, Stephanie A Amici, Kyle A Jablonski, Himanshu Savardekar, Amanda R Panfil, Linsen Li, Wei Zhou, Kevin Peine, Vrajesh Karkhanis, Eric M Bachelder, Kristy M Ainslie, Patrick L Green, Chenglong Li, Robert A Baiocchi, Mireia Guerau-de-Arellano
In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell-mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087238/lymphocyte-circadian-clocks-control-lymph-node-trafficking-and-adaptive-immune-responses
#2
David Druzd, Olga Matveeva, Louise Ince, Ute Harrison, Wenyan He, Christoph Schmal, Hanspeter Herzel, Anthony H Tsang, Naoto Kawakami, Alexei Leliavski, Olaf Uhl, Ling Yao, Leif Erik Sander, Chien-Sin Chen, Kerstin Kraus, Alba de Juan, Sophia Martina Hergenhan, Marc Ehlers, Berthold Koletzko, Rainer Haas, Werner Solbach, Henrik Oster, Christoph Scheiermann
Lymphocytes circulate through lymph nodes (LN) in search for antigen in what is believed to be a continuous process. Here, we show that lymphocyte migration through lymph nodes and lymph occurred in a non-continuous, circadian manner. Lymphocyte homing to lymph nodes peaked at night onset, with cells leaving the tissue during the day. This resulted in strong oscillations in lymphocyte cellularity in lymph nodes and efferent lymphatic fluid. Using lineage-specific genetic ablation of circadian clock function, we demonstrated this to be dependent on rhythmic expression of promigratory factors on lymphocytes...
January 6, 2017: Immunity
https://www.readbyqxmd.com/read/28086920/absence-of-system-xc-on-immune-cells-invading-the-central-nervous-system-alleviates-experimental-autoimmune-encephalitis
#3
Ellen Merckx, Giulia Albertini, Magdalena Paterka, Cathy Jensen, Philipp Albrecht, Michael Dietrich, Joeri Van Liefferinge, Eduard Bentea, Lise Verbruggen, Thomas Demuyser, Lauren Deneyer, Jan Lewerenz, Geert van Loo, Jacques De Keyser, Hideyo Sato, Pamela Maher, Axel Methner, Ann Massie
BACKGROUND: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System xc(-) or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration...
January 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28069965/dual-role-of-alcam-in-neuroinflammation-and-blood-brain-barrier-homeostasis
#4
Marc-André Lécuyer, Olivia Saint-Laurent, Lyne Bourbonnière, Sandra Larouche, Catherine Larochelle, Laure Michel, Marc Charabati, Michael Abadier, Stephanie Zandee, Neda Haghayegh Jahromi, Elizabeth Gowing, Camille Pittet, Ruth Lyck, Britta Engelhardt, Alexandre Prat
Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule found on blood-brain barrier endothelial cells (BBB-ECs) that was previously shown to be involved in leukocyte transmigration across the endothelium. In the present study, we found that ALCAM knockout (KO) mice developed a more severe myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis (EAE). The exacerbated disease was associated with a significant increase in the number of CNS-infiltrating proinflammatory leukocytes compared with WT controls...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28065579/roles-of-regulatory-t-cells-and-il-10-in-virus-induced-demyelination
#5
REVIEW
Stanley Perlman, Jingxian Zhao
Neurotropic viruses are important causes of morbidity and mortality in human populations. Some of these viruses preferentially infect oligodendrocytes in the white matter, causing either direct lysis of infected cells, or more commonly myelin damage as a consequence of the host immune response to the virus. Virus-induced demyelination has similarities to the human disease multiple sclerosis. To study this disease process in experimental animals, mice are infected, most commonly, with neurotropic strains of mouse hepatitis virus, a coronavirus or Theiler's murine encephalomyelitis, a picornavirus...
January 4, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28063054/high-dimensional-cytometry-of-central-nervous-system-leukocytes-during-neuroinflammation
#6
Dunja Mrdjen, Felix J Hartmann, Burkhard Becher
Autoimmune diseases like multiple sclerosis (MS) develop from the activation and complex interactions of a wide network of immune cells, which penetrate the central nervous system (CNS) and cause tissue damage and neurological deficits. Experimental autoimmune encephalomyelitis (EAE) is a model used to study various aspects of MS, including the infiltration of autoaggressive T cells and pathogenic, inflammatory myeloid cells into the CNS. Various signature landscapes of immune cell infiltrates have proven useful in shedding light on the causes of specific EAE symptoms in transgenic mice...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28060303/an-in-vitro-model-of-the-blood-brain-barrier-using-impedance-spectroscopy-a-focus-on-t-cell-endothelial-cell-interaction
#7
Ivan Kuzmanov, Alexander M Herrmann, Hans-Joachim Galla, Sven G Meuth, Heinz Wiendl, Luisa Klotz
Breakdown of the blood-brain barrier (BBB) is a critical step in the development of autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). This process is characterized by the transmigration of activated T cells across brain endothelial cells (ECs), the main constituents of the BBB. However, the consequences on brain EC function upon interaction with such T cells are largely unknown. Here we describe an assay that allows for the evaluation of primary mouse brain microvascular EC (MBMEC) function and barrier integrity during the interaction with T cells over time...
December 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28057805/cns-targeted-autoimmunity-leads-to-increased-influenza-mortality-in-mice
#8
Justin D Glenn, Matthew D Smith, Pei Xue, Yee Chan-Li, Samuel Collins, Peter A Calabresi, Maureen R Horton, Katharine A Whartenby
The discovery that central nervous system (CNS)-targeted autoreactive T cells required a process of licensing in the lung revealed an unexpected relationship between these organs. The clinical and immunological significance of this finding is bidirectional in that it showed not only a mechanism by which T cells become pathogenic before entering the CNS, but also the potential for this process to influence lung immunity as well. Epidemiological studies have shown that people with multiple sclerosis (MS) suffer from increased morbidity and mortality from infectious diseases, independent of immunosuppressive therapies...
January 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28057537/the-chloride-co-transporters-nkcc1-and-kcc2-in-experimental-autoimmune-encephalomyelitis-eae
#9
Muhammad Saad Yousuf, Kasia Zubkow, Gustavo Tenorio, Bradley Kerr
Patients with multiple sclerosis (MS) often complain of neuropathic pain. According to the Gate Control Theory of Pain, spinal networks of GABAergic inhibitory interneurons are important in modulating nociceptive inputs from the periphery. Na+-K+-2Cl- co-transporter 1 (NKCC1) and K+-Cl- co-transporter 2 (KCC2) generally dictate the tone of GABA/glycine inhibition by regulating intracellular chloride concentrations. In this study, we investigated the role of NKCC1 and KCC2 in neuropathic pain observed in the animal model, experimental autoimmune encephalomyelitis (EAE), a commonly used model to study the pathophysiology of MS...
January 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28056806/suppression-of-experimental-autoimmune-encephalomyelitis-by-ultraviolet-light-is-not-mediated-by-isomerization-of-urocanic-acid
#10
Amy A Irving, Steven J Marling, Lori A Plum, Hector F DeLuca
BACKGROUND: Ultraviolet B irradiation confers strong resistance against experimental autoimmune encephalomyelitis, a model of multiple sclerosis. This protection by ultraviolet B is independent of vitamin D production but causes isomerization of urocanic acid, a naturally occurring immunosuppressant. METHODS: To determine whether UCA isomerization from trans to cis is responsible for the protection against experimental autoimmune encephalomyelitis afforded by ultraviolet B, trans- or cis-urocanic acid was administered to animals and their disease progression was monitored...
January 5, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28052250/ebi2-expression-and-function-robust-in-memory-lymphocytes-and-increased-by-natalizumab-in-multiple-sclerosis
#11
Aurélie S Clottu, Amandine Mathias, Andreas W Sailer, Myriam Schluep, Jörg D Seebach, Renaud Du Pasquier, Caroline Pot
The interaction between oxysterols and the G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2) fine-tunes immune cell migration, a mechanism efficiently targeted by several disease-modifying treatments developed to treat multiple sclerosis (MS), such as natalizumab. We previously showed that memory CD4(+) T lymphocytes migrate specifically in response to 7α,25-dihydroxycholesterol (7α,25-OHC) via EBI2 in the MS murine model experimental autoimmune encephalomyelitis. However, the EBI2 expression profile in human lymphocytes in both healthy and MS donors is unknown...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28052249/opposing-functions-of-microglial-and-macrophagic-tnfr2-in-the-pathogenesis-of-experimental-autoimmune-encephalomyelitis
#12
Han Gao, Matt C Danzi, Claire S Choi, Mehran Taherian, Camilla Dalby-Hansen, Ditte G Ellman, Pernille M Madsen, John L Bixby, Vance P Lemmon, Kate L Lambertsen, Roberta Brambilla
In multiple sclerosis (MS), soluble tumor necrosis factor (TNF) is detrimental via activation of TNF receptor 1 (TNFR1), whereas transmembrane TNF is beneficial primarily by activating TNF receptor 2 (TNFR2). Here, we investigate the role of TNFR2 in microglia and monocytes/macrophages in experimental autoimmune encephalomyelitis (EAE), a model of MS, by cell-specific gene targeting. We show that TNFR2 ablation in microglia leads to early onset of EAE with increased leukocyte infiltration, T cell activation, and demyelination in the central nervous system (CNS)...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28049829/glucocorticoid-receptor-in-t-cells-mediates-protection-from-autoimmunity-in-pregnancy
#13
Jan Broder Engler, Nina Kursawe, María Emilia Solano, Kostas Patas, Sabine Wehrmann, Nina Heckmann, Fred Lühder, Holger M Reichardt, Petra Clara Arck, Stefan M Gold, Manuel A Friese
Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In vitro, we found the pregnancy hormone progesterone to robustly increase Treg frequencies via promiscuous binding to the glucocorticoid receptor (GR) in T cells...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28043135/screening-immunomodulators-to-skew-the-antigen-specific-autoimmune-response
#14
Laura Northrup, Bradley P Sullivan, Brittany L Hartwell, Aaron Garza, Cory Berkland
Current therapies to treat autoimmune diseases often result in side effects such as nonspecific immunosuppression. Therapies that can induce antigen-specific immune tolerance provide an opportunity to reverse autoimmunity and mitigate the risks associated with global immunosuppression. In an effort to induce antigen-specific immune tolerance, co-administration of immunomodulators with autoantigens has been investigated in an effort to reprogram autoimmunity. To date, identifying immunomodulators that may skew the antigen-specific immune response has been ad hoc at best...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28040492/valproic-acid-and-ask1-deficiency-ameliorate-optic-neuritis-and-neurodegeneration-in-an-animal-model-of-multiple-sclerosis
#15
Yuriko Azuchi, Atsuko Kimura, Xiaoli Guo, Goichi Akiyama, Takahiko Noro, Chikako Harada, Atsuko Nishigaki, Kazuhiko Namekata, Takayuki Harada
Optic neuritis, which is an acute inflammatory demyelinating syndrome of the central nervous system, is one of the major complications in multiple sclerosis (MS). Herein, we investigated the therapeutic potential of valproic acid (VPA) on optic neuritis in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. EAE was induced in C57BL/6 mice by immunization with MOG35-55 and VPA (300mg/kg) was administered via intraperitoneal injection once daily from day 3 postimmunization until the end of the experimental period (day 28)...
December 28, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28039299/hyperactivation-of-the-nlrp3-inflammasome-in-myeloid-cells-leads-to-severe-organ-damage-in-experimental-lupus
#16
Ailing Lu, Hua Li, Junling Niu, Shuxian Wu, Guang Xue, Xiaomin Yao, Qiuhong Guo, Nianhong Wan, Paride Abliz, Guiwen Yang, Liguo An, Guangxun Meng
Systemic lupus erythematosus (SLE) is an autoimmune syndrome associated with severe organ damage resulting from the activation of immune cells. Recently, a role for caspase-1 in murine lupus was described, indicating an involvement of inflammasomes in the development of SLE. Among multiple inflammasomes identified, the NLRP3 inflammasome was connected to diverse diseases, including autoimmune encephalomyelitis. However, the function of NLRP3 in SLE development remains elusive. In this study, we explored the role of NLRP3 in the development of SLE using the pristane-induced experimental lupus model...
December 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28038358/il-22-promotes-fas-expression-in-oligodendrocytes-and-inhibits-foxp3-expression-in-t-cells-by-activating-the-nf-%C3%AE%C2%BAb-pathway-in-multiple-sclerosis
#17
Jin Zhen, Jun Yuan, Yongwang Fu, Runxiu Zhu, Meiling Wang, Hong Chang, Yan Zhao, Dong Wang, Zuneng Lu
Multiple sclerosis (MS) is characterized by an increase in interleukin-22 and Fas, and a decrease in FOXP3, among other factors. In this study, we examined patients with MS and healthy control subjects and used the experimental autoimmune encephalomyelitis (EAE) animal model to identify the effects of IL-22 on oligodendrocytes and T cells in MS development. In MS, the expression of Fas in oligodendrocytes and IL-22 in CD4(+)CCR4(+)CCR6(+)CCR10(+) T cells was enhanced. Ikaros and FOXP3 were both decreased in T cells...
December 27, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/28030334/trichuris-suis-secrete-products-that-reduce-disease-severity-in-a-multiple-sclerosis-model
#18
Christine Søholm Hansen, Henrik Hasseldam, Idahella Hyldgaard Bacher, Stig Milan Thamsborg, Flemming Fryd Johansen, Helene Kringel
Multiple sclerosis is a chronic inflammatory central nervous system (CNS) disease, which affects about 1 in 1000 individuals in the western world. It has been suggested that this relatively high prevalence is linked to a high level of hygiene, i.e. a reduced exposure to various microorganisms, including parasites. Parasites are known to employ different immunomodulatory and antiinflammatory strategies, which enable them to evade destruction by the immune system. We have investigated the immunomodulation by the swine whipworm, Trichuris suis, by measuring the impact of oral administration of T...
March 1, 2017: Acta Parasitologica
https://www.readbyqxmd.com/read/28028151/lrch1-interferes-with-dock8-cdc42-induced-t-cell-migration-and-ameliorates-experimental-autoimmune-encephalomyelitis
#19
Xiaoyan Xu, Lei Han, Guixian Zhao, Shengjie Xue, Yunzhen Gao, Jun Xiao, Shicheng Zhang, Peng Chen, Zhi-Ying Wu, Jianping Ding, Ronggui Hu, Bin Wei, Hongyan Wang
Directional autoreactive CD4(+) T cell migration into the central nervous system plays a critical role in multiple sclerosis. Recently, DOCK8 was identified as a guanine-nucleotide exchange factor (GEF) for Cdc42 activation and has been associated with human mental retardation. Little is known about whether DOCK8 is related to multiple sclerosis (MS) and how to restrict its GEF activity. Using two screening systems, we found that LRCH1 competes with Cdc42 for interaction with DOCK8 and restrains T cell migration...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28025778/role-of-mast-cells-in-the-pathogenesis-of-multiple-sclerosis-and-experimental-autoimmune-encephalomyelitis
#20
REVIEW
Daniel Elieh-Ali-Komi, Yonghao Cao
Multiple sclerosis (MS) is a neurological autoimmune disorder of the central nervous system (CNS), characterized by recurrent episodes of inflammatory demyelination and consequent axonal deterioration. The hallmark of the disease is the demyelinated plaque, a hypocellular area characterized by formation of astrocytic scars and infiltration of mononuclear cells. Recent studies have revealed that both innate and adaptive immune cells contribute to the pathogenesis of MS and its experimental autoimmune encephalomyelitis (EAE) model...
December 26, 2016: Clinical Reviews in Allergy & Immunology
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