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multiple sclerosis and dendritic cells

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https://www.readbyqxmd.com/read/28063629/the-autoimmune-risk-gene-zmiz1-is-a-vitamin-d-responsive-marker-of-a-molecular-phenotype-of-multiple-sclerosis
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
November 15, 2016: Immunology
https://www.readbyqxmd.com/read/27836182/myeloid-dendritic-cells-exhibit-defects-in-activation-and-function-in-patients-with-multiple-sclerosis
#7
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
#8
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 3, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/27799933/ectopic-lymphoid-structures-powerhouse-of-autoimmunity
#9
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
#10
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
https://www.readbyqxmd.com/read/27708418/b-cell-derived-transforming-growth-factor-%C3%AE-1-expression-limits-the-induction-phase-of-autoimmune-neuroinflammation
#11
Kristbjörg Bjarnadóttir, Mahdia Benkhoucha, Doron Merkler, Martin S Weber, Natalie L Payne, Claude C A Bernard, Nicolas Molnarfi, Patrice H Lalive
Studies in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), have shown that regulatory B cells modulate the course of the disease via the production of suppressive cytokines. While data indicate a role for transforming growth factor (TGF)-β1 expression in regulatory B cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B-TGF-β1(-/-)) were tested in EAE induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG)...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27704036/treatment-of-spontaneous-eae-by-laquinimod-reduces-tfh-b-cell-aggregates-and-disease-progression
#12
Michel Varrin-Doyer, Kara L Pekarek, Collin M Spencer, Claude C A Bernard, Raymond A Sobel, Bruce A C Cree, Ulf Schulze-Topphoff, Scott S Zamvil
OBJECTIVE: To evaluate the influence of oral laquinimod, a candidate multiple sclerosis (MS) treatment, on induction of T follicular helper cells, development of meningeal B cell aggregates, and clinical disease in a spontaneous B cell-dependent MS model. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by immunization with recombinant myelin oligodendrocyte glycoprotein (rMOG) protein. Spontaneous EAE was evaluated in C57BL/6 MOG p35-55-specific T cell receptor transgenic (2D2) × MOG-specific immunoglobulin (Ig)H-chain knock-in (IgH(MOG-ki) [Th]) mice...
October 2016: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/27703987/immunomodulatory-effects-of-1-25-dihydroxyvitamin-d3-on-dendritic-cells-promote-induction-of-t-cell-hyporesponsiveness-to-myelin-derived-antigens
#13
Wai-Ping Lee, Barbara Willekens, Patrick Cras, Herman Goossens, Eva Martínez-Cáceres, Zwi N Berneman, Nathalie Cools
While emerging evidence indicates that dendritic cells (DC) play a central role in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory agents provides prospect as disease-modifying therapy. Our observations reveal that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment of monocyte-derived DC results in a semimature phenotype and anti-inflammatory cytokine profile as compared to conventional DC, in both healthy controls and MS patients. Importantly, 1,25(OH)2D3-treated DC induce T cell hyporesponsiveness, as demonstrated in an allogeneic mixed leukocyte reaction...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27579996/design-of-polyelectrolyte-multilayers-to-promote-immunological-tolerance
#14
Lisa H Tostanoski, Yu-Chieh Chiu, James I Andorko, Ming Guo, Xiangbin Zeng, Peipei Zhang, Walter Royal Iii, Christopher M Jewell
Recent studies demonstrate that excess signaling through inflammatory pathways (e.g., toll-like receptors, TLRs) contributes to the pathogenesis of human autoimmune diseases, including lupus, diabetes, and multiple sclerosis (MS). We hypothesized that co-delivery of a regulatory ligand of TLR9, GpG oligonucleotide, along with myelin - the "self" molecule attacked in MS - might restrain the pro-inflammatory signaling typically present during myelin presentation, redirecting T cell differentiation away from inflammatory populations and towards tolerogenic phenotypes such as regulatory T cells...
August 31, 2016: ACS Nano
https://www.readbyqxmd.com/read/27536199/mature-dendritic-cells-cause-th17-treg-imbalance-by-secreting-tgf-%C3%AE-1-and-il-6-in-the-pathogenesis-of-experimental-autoimmune-encephalomyelitis
#15
Pingxia Lu, Yingping Cao, Meihua Wang, Peizheng Zheng, Juan Hou, Chanhong Zhu, Jianda Hu
Multiple sclerosis (MS) is generally acknowledged to be an autoimmune disease, but its etiology remains unknown. The most intensively studied animal model of MS is experimental autoimmune encephalomyelitis (EAE). Dendritic cells (DCs), the professional antigen presenting cells (APCs), have gained increasing attention because they connect innate and adaptive immunity. The aim of this study was to determine the role of mature DCs in the pathogenesis of EAE. It was found that the number of mature DCs in the EAE spleen increased compared to the control group (p < 0...
2016: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/27514287/myeloid-cells-targets-of-medication-in-multiple-sclerosis
#16
REVIEW
Manoj K Mishra, V Wee Yong
Discussions of multiple sclerosis (MS) pathophysiology tend to focus on T cells and B cells of the adaptive immune response. The innate immune system is less commonly considered in this context, although dendritic cells, monocytes, macrophages and microglia - collectively referred to as myeloid cells - have prominent roles in MS pathogenesis. These populations of myeloid cells function as antigen-presenting cells and effector cells in neuroinflammation. Furthermore, a vicious cycle of interactions between T cells and myeloid cells exacerbates pathology...
September 2016: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/27499754/utilization-of-dimethyl-fumarate-and-related-molecules-for-treatment-of-multiple-sclerosis-cancer-and-other-diseases
#17
REVIEW
Zaidoon Al-Jaderi, Azzam A Maghazachi
Several drugs have been approved for treatment of multiple sclerosis (MS). Dimethyl fumarate (DMF) is utilized as an oral drug to treat this disease and is proven to be potent with less side effects than several other drugs. On the other hand, monomethyl fumarate (MMF), a related compound, has not been examined in greater details although it has the potential as a therapeutic drug for MS and other diseases. The mechanism of action of DMF or MMF is related to their ability to enhance the antioxidant pathways and to inhibit reactive oxygen species...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27479807/tgf%C3%AE-regulates-persistent-neuroinflammation-by-controlling-th1-polarization-and-ros-production-via-monocyte-derived-dendritic-cells
#18
Roham Parsa, Harald Lund, Ivana Tosevski, Xing-Mei Zhang, Ursula Malipiero, Jan Beckervordersandforth, Doron Merkler, Marco Prinz, Alexandra Gyllenberg, Tojo James, Andreas Warnecke, Jan Hillert, Lars Alfredsson, Ingrid Kockum, Tomas Olsson, Adriano Fontana, Tobias Suter, Robert A Harris
Intracerebral levels of Transforming Growth Factor beta (TGFβ) rise rapidly during the onset of experimental autoimmune encephalomyelitis (EAE), a mouse model of Multiple Sclerosis (MS). We addressed the role of TGFβ responsiveness in EAE by targeting the TGFβ receptor in myeloid cells, determining that Tgfbr2 was specifically targeted in monocyte-derived dendritic cells (moDCs) but not in CNS resident microglia by using bone-marrow chimeric mice. TGFβ responsiveness in moDCs was necessary for the remission phase since LysM(Cre) Tgfbr2(fl/fl) mice developed a chronic form of EAE characterized by severe demyelination and extensive infiltration of activated moDCs in the CNS...
November 2016: Glia
https://www.readbyqxmd.com/read/27417417/the-er-membrane-anchored-ubiquitin-ligase-hrd1-is-a-positive-regulator-of-t-cell-immunity
#19
Yuanming Xu, Fang Zhao, Quan Qiu, Kun Chen, Juncheng Wei, Qingfei Kong, Beixue Gao, Johanna Melo-Cardenas, Bin Zhang, Jinping Zhang, Jianxun Song, Donna D Zhang, Jianing Zhang, Yunping Fan, Huabin Li, Deyu Fang
Identification of positive regulators of T-cell immunity induced during autoimmune diseases is critical for developing novel therapies. The endoplasmic reticulum resident ubiquitin ligase Hrd1 has recently emerged as a critical regulator of dendritic cell antigen presentation, but its role in T-cell immunity is unknown. Here we show that genetic deletion of Hrd1 in mice inhibits T-cell proliferation, production of IL-2, and differentiation of Th1 and Th17 cells, and consequently protects mice from experimental autoimmune encephalomyelitis...
July 15, 2016: Nature Communications
https://www.readbyqxmd.com/read/27416719/-multiple-sclerosis-vaccine-possibilities-of-the-use-of-dendritic-cells-immunomodulatory-potential
#20
M M Odinak, G N Bisaga, V S Chirskii, M V Pashchenkov, I A Baldueva, V M Moiseenko, T L Nekhaeva, N M Kalinina, N I Davydova, N V Bychkova, A V Pozdnyakov
For the first time we carried out a clinical assessment of the safety, tolerability and clinical efficacy course of repeated administration of experimental modified autologous vaccine interleykin (IL-10) dendritic cells in two patients with secondary-progressive multiple sclerosis patient and one with relapsing-remitting multiple sclerosis. In the course of treatment, we carried out clinical and immunological monitoring. It was found out that intradermal dose of 3 x 10⁶ cells applied to spinal area 6-12. times did not cause any serious side effects...
April 2016: Voenno-medit︠s︡inskiĭ Zhurnal
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