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multiple sclerosis and dendritic cells

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https://www.readbyqxmd.com/read/28342735/inhibition-of-effector-antigen-specific-t-cells-by-intradermal-administration-of-heme-oxygenase-1-inducers
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/27861821/effects-of-c2ta-genetic-polymorphisms-on-mhc-class-ii-expression-and-autoimmune-diseases
#16
Anthony C Y Yau, Fredrik Piehl, Tomas Olsson, Rikard Holmdahl
Antigen presentation by the MHC-II to CD4(+) T cells is important in adaptive immune responses. The class II transactivator (CIITA in human and C2TA in mouse) is the master regulator of MHC-II gene expression. It coordinates the transcription factors necessary for the transcription of MHC-II molecules. In humans, genetic variations in CIITA have been associated with differential expression of MHC-II and susceptibility to autoimmune diseases. Here we made use of a C2ta congenic mouse strain (expressing MHC-II haplotype H-2(q) ) to investigate the effect of the natural genetic polymorphisms in type I promoter of C2ta on MHC-II expression and function...
April 2017: Immunology
https://www.readbyqxmd.com/read/27836182/myeloid-dendritic-cells-exhibit-defects-in-activation-and-function-in-patients-with-multiple-sclerosis
#17
Jürgen Haas, Alexander Schwarz, Mirjam Korporal-Kuhnke, Sven Jarius, Brigitte Wildemann
BACKGROUND: Regulatory T cells (Tregs) are functionally defective in patients with multiple sclerosis (MS) and this dysfunction is related to an imbalanced composition of naïve and memory Treg subtypes. Several lines of evidence indicate that these abnormalities might result from a premature decline in thymic-dependent Treg neogenesis. Myeloid dendritic cells (mDCs) critically determine Treg differentiation in the thymus, and thymic stromal lymphopoietin receptor (TSLPR) expressed on mDCs is a key component of the signaling pathways involved in this process...
December 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27811337/patients-with-multiple-sclerosis-demonstrate-reduced-subbasal-corneal-nerve-fibre-density
#18
Janine Mikolajczak, Hanna Zimmermann, Ahmad Kheirkhah, Ella Maria Kadas, Timm Oberwahrenbrock, Rodrigo Muller, Aiai Ren, Joseph Kuchling, Holger Dietze, Harald Prüss, Friedemann Paul, Pedram Hamrah, Alexander U Brandt
BACKGROUND: Many studies in multiple sclerosis (MS) have investigated the retina. Little, however, is known about the effect of MS on the cornea, which is innervated by the trigeminal nerve. It is the site of neural-immune interaction with local dendritic cells reacting in response to environmental stimuli. OBJECTIVE: This study aims to investigate the effect of MS on corneal nerve fibres and dendritic cells in the subbasal nerve plexus using in vivo confocal microscopy (IVCM)...
November 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/27799933/ectopic-lymphoid-structures-powerhouse-of-autoimmunity
#19
REVIEW
Elisa Corsiero, Alessandra Nerviani, Michele Bombardieri, Costantino Pitzalis
Ectopic lymphoid structures (ELS) often develop at sites of inflammation in target tissues of autoimmune diseases, such as rheumatoid arthritis, Sjögren's syndrome, multiple sclerosis, myasthenia gravis, and systemic lupus erythematosus. ELS are characterized by the formation of organized T/B cells aggregates, which can acquire follicular dendritic cells network supporting an ectopic germinal center response. In this review, we shall summarize the mechanisms that regulate the formation of ELS in tertiary lymphoid organs, with particular emphasis on the role of lymphoid chemokines in both formation and maintenance of ELS, the role of emerging positive and negative regulators of ELS development and function, including T follicular helper cells and IL-27, respectively...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27766281/alemtuzumab-treatment-alters-circulating-innate-immune-cells-in-multiple-sclerosis
#20
Catharina C Gross, Diana Ahmetspahic, Tobias Ruck, Andreas Schulte-Mecklenbeck, Kathrin Schwarte, Silke Jörgens, Stefanie Scheu, Susanne Windhagen, Bettina Graefe, Nico Melzer, Luisa Klotz, Volker Arolt, Heinz Wiendl, Sven G Meuth, Judith Alferink
OBJECTIVE: To characterize changes in myeloid and lymphoid innate immune cells in patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment. METHODS: Circulating innate immune cells including myeloid cells and innate lymphoid cells (ILCs) were analyzed before and 6 and 12 months after onset of alemtuzumab treatment. Furthermore, a potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-23 production by myeloid cells and natural killer (NK) cell cytolytic activity was determined...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
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