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multiple sclerosis and dendritic cells

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https://www.readbyqxmd.com/read/28421248/indications-for-cellular-migration-from-the-central-nervous-system-to-its-draining-lymph-nodes-in-cd11c-gfp-bone-marrow-chimeras-following-eae
#1
Fridtjof Schiefenhövel, Kerstin Immig, Carolin Prodinger, Ingo Bechmann
The concept as to how the brain maintains its immune privilege has initially been based on observations that it is lacking classical lymph vessels and later, the absence of dendritic cells (DC). This view has been challenged by several groups demonstrating drainage/migration of injected tracers and cells into cervical lymph nodes (CLNs) and the presence of brain antigens in CLNs in the course of various brain pathologies. Using CD11c-diphtheria toxin receptor (DTR)-green fluorescent protein (GFP) transgenic (tg) mice, we have shown the existence of CD11c(+) cells, a main DC marker, within the brain parenchyma...
April 18, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28409282/motor-neuron-vulnerability-and-resistance-in-amyotrophic-lateral-sclerosis
#2
REVIEW
Jik Nijssen, Laura H Comley, Eva Hedlund
In the fatal disease-amyotrophic lateral sclerosis (ALS)-upper (corticospinal) motor neurons (MNs) and lower somatic MNs, which innervate voluntary muscles, degenerate. Importantly, certain lower MN subgroups are relatively resistant to degeneration, even though pathogenic proteins are typically ubiquitously expressed. Ocular MNs (OMNs), including the oculomotor, trochlear and abducens nuclei (CNIII, IV and VI), which regulate eye movement, persist throughout the disease. Consequently, eye-tracking devices are used to enable paralysed ALS patients (who can no longer speak) to communicate...
April 13, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28388685/fetuin-a-deficiency-protects-mice-from-experimental-autoimmune-encephalomyelitis-eae-and-correlates-with-altered-innate-immune-response
#3
Violaine K Harris, Lena Bell, Ruth-Anne Langan, John Tuddenham, Mark Landy, Saud A Sadiq
Fetuin-A is a biomarker of disease activity in multiple sclerosis. Our aim was to investigate whether Fetuin-A plays a direct role in the neuroinflammatory response in the mouse EAE model. Peak Fetuin-A expression in the CNS and in peripheral lymphoid tissue correlated with peak EAE disease activity. Fetuin-A-deficient mice showed reduced EAE severity associated with an accumulation of splenic monocyte and dendritic cell populations, increased IL-12p40, ASC1, and IL-1β expression, and an increase in T regulatory cells...
2017: PloS One
https://www.readbyqxmd.com/read/28363955/dendritic-cells-engineered-to-overexpress-25-hydroxyvitamin-d-1%C3%AE-hydroxylase-and-pulsed-with-a-myelin-antigen-provide-myelin-specific-suppression-of-ongoing-experimental-allergic-encephalomyelitis
#4
Chih-Huang Li, Jintao Zhang, David J Baylink, Xiaohua Wang, Naga Bharani Goparaju, Yi Xu, Samiksha Wasnik, Yanmei Cheng, Edmundo Carreon Berumen, Xuezhong Qin, Kin-Hing William Lau, Xiaolei Tang
Multiple sclerosis (MS) is caused by immune-mediated damage of myelin sheath. Current therapies aim to block such immune responses. However, this blocking is not sufficiently specific and hence compromises immunity, leading to severe side effects. In addition, blocking medications usually provide transient effects and require frequent administration, which further increases the chance to compromise immunity. In this regard, myelin-specific therapy may provide the desired specificity and a long-lasting therapeutic effect by inducing myelin-specific regulatory T (Treg) cells...
March 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28356656/cpg-type-a-induction-of-an-early-protective-environment-in-experimental-multiple-sclerosis
#5
James Crooks, Marco Gargaro, Carmine Vacca, Claudia Volpi, Matteo Pirro, Giulia Scalisi, Antonella Turco, Rita Romani, Davide Matino, Abdolmohamad Rostami, Paolo Puccetti, Bruno Gran, Francesca Fallarino
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS), and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4(+) T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs), typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs)...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28342735/inhibition-of-effector-antigen-specific-t-cells-by-intradermal-administration-of-heme-oxygenase-1-inducers
#6
Thomas Simon, Julien Pogu, Séverine Rémy, Frédéric Brau, Sylvie Pogu, Maud Maquigneau, Jean-François Fonteneau, Nicolas Poirier, Bernard Vanhove, Gilles Blancho, Eliane Piaggio, Ignacio Anegon, Philippe Blancou
Developing protocols aimed at inhibiting effector T cells would be key for the treatment of T cell-dependent autoimmune diseases including type 1 autoimmune diabetes (T1D) and multiple sclerosis (MS). While heme oxygenase-1 (HO-1) inducers are clinically approved drugs for non-immune-related diseases, they do have immunosuppressive properties when administered systemically in rodents. Here we show that HO-1 inducers inhibit antigen-specific effector T cells when injected intradermally together with the T cell cognate antigens in mice...
March 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28289417/murine-cytomegalovirus-infection-induces-susceptibility-to-eae-in-resistant-balb-c-mice
#7
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/28283756/dopamine-t-cells-and-multiple-sclerosis-ms
#8
REVIEW
Mia Levite, Franca Marino, Marco Cosentino
Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others...
March 10, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28272439/discovery-of-bvdu-as-a-promising-drug-for-autoimmune-diseases-therapy-by-dendritic-cell-based-functional-screening
#9
Shuai Chen, Jinfeng Zhou, Yingying Cai, Xinyuan Zheng, Sirong Xie, Yuhan Liao, Yu Zhu, Chaoyan Qin, Weiming Lai, Cuixia Yang, Xin Xie, Changsheng Du
Dendritic cells (DCs) play a critical role in the pathogenesis of autoimmune diseases including multiple sclerosis, and targeting DCs' cytokines production is an important strategy for autoimmune diseases treatment. By establishing a high-throughput screening system, we analyzed LOPAC drug library to identify drugs that control the secretion of IL-6 by DCs, we selected the most likely candidate drug, BVDU, and found that it affected not only IL-6 production, but also that of IL-12, IL-1β during the DCs differentiation and maturation...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28250776/allogeneic-adipose-derived-mesenchymal-stromal-cells-ameliorate-experimental-autoimmune-encephalomyelitis-by-regulating-self-reactive-t-cell-responses-and-dendritic-cell-function
#10
Per Anderson, Elena Gonzalez-Rey, Francisco O'Valle, Francisco Martin, F Javier Oliver, Mario Delgado
Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS). Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs) in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs) suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 1/2 activities...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28238951/oral-administration-of-the-nitroxide-radical-tempol-exhibits-immunomodulatory-and-therapeutic-properties-in-multiple-sclerosis-models
#11
Sarah Neil, Jaebong Huh, Victoria Baronas, Xinhui Li, Henry F McFarland, Murali Cherukuri, James B Mitchell, Jacqueline A Quandt
Therapies with both immunomodulatory and neuroprotective properties are thought to have the greatest promise in reducing the severity and progression of multiple sclerosis (MS). Several reactive oxygen (ROS) and reactive nitrogen species (RNS) are implicated in inflammatory-mediated damage to the central nervous system (CNS) in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) is a stable nitroxide radical with potent antioxidant activity...
February 24, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28201972/cell-based-tolerogenic-therapy-experience-from-animal-models-of-multiple-sclerosis-type-1-diabetes-and-rheumatoid-arthritis
#12
Ivana Stojanović, Mirjana Dimitrijević, Marta Vives-Pi, Maria Jose Mansilla, Irma Pujol-Autonell, Silvia Rodríguez-Fernandez, Lenka Palová-Jelínková, David P Funda, Alisa Gruden-Movsesijan, Ljiljana Sofronić-Milosavljević, Catharien M U Hilkens, Eva Martínez-Cáceres, Djordje Miljković
Cell-based tolerogenic therapy is a promising approach for the treatment of autoimmune diseases and transplant rejection. Regulatory T cells and tolerogenic dendritic cells have been particularly explored in the treatment of various autoimmune disorders in experimental models of disease. Although some of these cells have already been tested in a limited number of clinical trials, there is still a need for preclinical research on tolerogenic cells in animal models of autoimmunity. This review will focus on the relevance of data obtained from studies in experimental animal models for the use of tolerogenic cell-based therapy in humans...
February 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28179539/smoking-reduces-circulating-cd26-hi-cd161-hi-mait-cells-in-healthy-individuals-and-patients-with-multiple-sclerosis
#13
Cecilie Ammitzbøll, Lars Börnsen, Jeppe Romme Christensen, Rikke Ratzer, Birgitte Romme Nielsen, Helle B Søndergaard, Marina R von Essen, Finn Sellebjerg
Upon chronic cigarette smoke exposure, inhaled antigens and irritants cause altered lung immune homeostasis. Circulating immune cells are affected, and smoking is associated with an increased risk of developing various disorders, including multiple sclerosis (MS). This study was conducted to determine the impact of smoking on circulating immune cell subsets. Furthermore, we determined whether any smoking-associated changes were related to MS. With the use of flow cytometry, CFSE assays, and ELISpot assays, we analyzed circulating immune cell phenotypes and quantified antigen-induced proliferation and cytokine secretion in smokers and nonsmokers in a cohort of 100 healthy individuals (HI)...
February 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28165507/paeoniflorin-ameliorates-experimental-autoimmune-encephalomyelitis-via-inhibition-of-dendritic-cell-function-and-th17-cell-differentiation
#14
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/28157168/regulation-of-t-cell-activation-and-differentiation-by-extracellular-vesicles-and-their-pathogenic-role-in-systemic-lupus-erythematosus-and-multiple-sclerosis
#15
REVIEW
Cristina Ulivieri, Cosima T Baldari
How autoreactive tissue-infiltrated effector T cells are induced and sustained in autoimmune disease, usually dominated by the Th1 and Th17 subsets, is still largely unknown. In organ-specific autoimmunity, self-reactive T cells initially activated by dendritic cells (DCs) in the lymph nodes migrate and infiltrate into the target tissues where their reactivation by peripheral tissue antigen is a prerequisite for effector cytokine production and tissue destruction. The target tissue microenvironment, as well as the local microenvironment at the immune synapse formed by T cells that encounter cognate antigen presenting cells (APCs) shave recently emerged as critical factors in shaping the differentiation and function of self-reactive effector T cells, providing the signals required for their activation in the form of the self-antigen and cytokine milieu...
February 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28063629/the-autoimmune-risk-gene-zmiz1-is-a-vitamin-d-responsive-marker-of-a-molecular-phenotype-of-multiple-sclerosis
#16
N L Fewings, P N Gatt, F C McKay, G P Parnell, S D Schibeci, J Edwards, M A Basuki, A Goldinger, M J Fabis-Pedrini, A G Kermode, C P Manrique, J L McCauley, D Nickles, S E Baranzini, T Burke, S Vucic, G J Stewart, D R Booth
Multiple Sclerosis (MS) is a neurological condition driven in part by immune cells from the peripheral circulation, the targets for current successful therapies. The autoimmune and MS risk gene ZMIZ1 is underexpressed in blood in people with MS. We show that, from three independent sets of transcriptomic data, expression of ZMIZ1 is tightly correlated with that of hundreds of other genes. Further we show expression is partially heritable (heritability 0.26), relatively stable over time, predominantly in plasmacytoid dendritic cells and non-classical monocytes, and that levels of ZMIZ1 protein expression are reduced in MS...
January 4, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27940382/polyplexes-assembled-from-self-peptides-and-regulatory-nucleic-acids-blunt-toll-like-receptor-signaling-to-combat-autoimmunity
#17
Krystina L Hess, James I Andorko, Lisa H Tostanoski, Christopher M Jewell
Autoimmune diseases occur when the immune system incorrectly recognizes self-molecules as foreign; in the case of multiple sclerosis (MS), myelin is attacked. Intriguingly, new studies reveal toll-like receptors (TLRs), pathways usually involved in generating immune responses against pathogens, play a significant role in driving autoimmune disease in both humans and animal models. We reasoned polyplexes formed from myelin self-antigen and regulatory TLR antagonists might limit TLR signaling during differentiation of myelin-specific T cells, inducing tolerance by biasing T cells away from inflammatory phenotypes...
February 2017: Biomaterials
https://www.readbyqxmd.com/read/27939246/knockout-of-p2y12-aggravates-experimental-autoimmune-encephalomyelitis-in-mice-via-increasing-of-il-23-production-and-th17-cell-differentiation-by-dendritic-cells
#18
Jiang Zhang, Zhenlong Li, Xuefei Hu, Qiong Su, Cong He, Jing Liu, Hua Ren, Min Qian, Junling Liu, Shufang Cui, Wenzheng Jiang
Experimental autoimmune encephalomyelitis (EAE), a common model of multiple sclerosis (MS), is mainly mediated by CD4(+) T cells with demyelination and neurodegeneration of central nervous system (CNS). The loss of P2Y12 receptor might be associated with the pathogenesis of MS/EAE, but its potential mechanism is still not clear. In this study, more severe EAE developed in P2Y12-knockout (P2Y12-KO) mice compared to WT mice. Knockout of P2Y12 increased expression of IL-17A in the sera and proportion of Th17 cells in spleen and CNS...
December 7, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#19
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27903432/antigen-presentation-for-priming-t-cells-in-central-system
#20
Shaoni Dasgupta, Subhajit Dasgupta
Generation of myelin antigen-specific T cells is a major event in neuroimmune responses that causes demyelination. The antigen-priming of T cells and its location is important in chronic and acute inflammation. In autoimmune multiple sclerosis, the effector T cells are considered to generate in periphery. However, the reasons for chronic relapsing-remitting events are obscure. Considering mechanisms, a feasible aim of research is to investigate the role of antigen-primed T cells in lupus cerebritis. Last thirty years of investigations emphasize the relevance of microglia and infiltrated dendritic cells/macrophages as antigen presenting cells in the central nervous system...
January 2017: International Journal of Biochemistry & Cell Biology
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