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multiple sclerosis and dendritic cells

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https://www.readbyqxmd.com/read/29774215/importance-of-functional-loss-of-fus-in-ftld-als
#1
REVIEW
Shinsuke Ishigaki, Gen Sobue
Fused in sarcoma (FUS) is an RNA binding protein that regulates RNA metabolism including alternative splicing, transcription, and RNA transportation. FUS is genetically and pathologically involved in frontotemporal lobar degeneration (FTLD)/amyotrophic lateral sclerosis (ALS). Multiple lines of evidence across diverse models suggest that functional loss of FUS can lead to neuronal dysfunction and/or neuronal cell death. Loss of FUS in the nucleus can impair alternative splicing and/or transcription, whereas dysfunction of FUS in the cytoplasm, especially in the dendritic spines of neurons, can cause mRNA destabilization...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29763776/dimethyl-fumarate-downregulates-the-immune-response-through-the-hca-2-gpr109a-pathway-implications-for-the-treatment-of-multiple-sclerosis
#2
REVIEW
Felipe von Glehn, Rafael P C Dias-Carneiro, Adriel S Moraes, Alessandro S Farias, Veronica A P G Silva, Francisco T M Oliveira, Carlos Eduardo B G Silva, Fabricio de Carvalho, Elaine Rahal, Clare Baecher-Allan, Leonilda M B Santos
BACKGROUND: The mechanisms of action of dimethyl fumarate (DMF), and its metabolite, monomethyl fumarate (MMF), for the treatment of multiple sclerosis are not completely elucidated. OBJECTIVES: To discuss the role of DMF/MMF-induced hydroxycarboxylic acid receptor 2 (HCA2 /GPR109A) pathway activation in the immune response and treatment of MS. METHODS: A narrative (traditional) review of the current literature. RESULTS: Studies have shown that binding of DMF/MMF to HCA2 on dendritic cells inhibits the production of pro-inflammatory cytokines in vitro and in MS murine models...
April 25, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29761344/beyond-the-magic-bullet-current-progress-of-therapeutic-vaccination-in-multiple-sclerosis
#3
Barbara Willekens, Nathalie Cools
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) characterized by neuroinflammation, neurodegeneration and impaired repair mechanisms that lead to neurological disability. The crux of MS is the patient's own immune cells attacking self-antigens in the CNS, namely the myelin sheath that protects nerve cells of the brain and spinal cord. Restoring antigen-specific tolerance via therapeutic vaccination is an innovative and exciting approach in MS therapy. Indeed, leveraging the body's attempt to prevent autoimmunity, i...
May 14, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29749614/microrna-signature-of-central-nervous-system-infiltrating-dendritic-cells-in-an-animal-model-of-multiple-sclerosis
#4
Mariah L Hoye, Angela S Archambault, Taylor M Gordon, Landon K Oetjen, Matthew D Cain, Robyn S Klein, Seth D Crosby, Brian S Kim, Timothy M Miller, Gregory F Wu
Innate immune cells are integral to the pathogenesis of several diseases of the central nervous system (CNS), including multiple sclerosis (MS). Dendritic cells (DCs) are potent CD11c+ antigen-presenting cells that are critical regulators of adaptive immune responses, particularly in autoimmune diseases such as MS. The regulation of DC function in both the periphery and CNS compartment has not been fully elucidated. One limitation to studying the role of CD11c+ DCs in the CNS is that microglia can upregulate CD11c during inflammation, making it challenging to distinguish bone marrow-derived DCs (BMDCs) from microglia...
May 10, 2018: Immunology
https://www.readbyqxmd.com/read/29733594/development-of-a-fluorescent-bodipy-probe-for-visualization-of-the-serotonin-5-ht1a-receptor-in-native-cells-of-the-immune-system
#5
Gloria Hernandez-Torres, Ernesto Enriquez Palacios, Miriam Mecha, Ana Feliu, Ainoa Rueda-Zubiaurre, Alba Angelina, Leticia Martin-Cruz, Mar Martín-Fontecha, Oscar Palomares, Carmen Guaza, Eduardo Peña-Cabrera, María L López-Rodríguez, Silvia Ortega-Gutierrez
Serotonin (5-HT) modulates key aspects of the immune system. However, its precise function and the receptors involved in the observed effects have remained elusive. Among the different serotonin receptors, 5-HT1A plays an important role in the immune system given its presence in cells involved in both the innate and the adaptive immune responses, but its actual levels of expression under different conditions have not been comprehensively studied due to the lack of suitable tools. To further clarify the role of 5-HT1A receptor in the immune system, we have developed a fluorescent small molecule probe that enables the direct study of the receptor levels in native cells...
May 7, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29729445/emerging-role-of-il-35-in-inflammatory-autoimmune-diseases
#6
REVIEW
Lin-Chong Su, Xiao-Yan Liu, An-Fang Huang, Wang-Dong Xu
Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis...
May 3, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29729246/oligodendrocyte-specific-loss-of-cdk5-disrupts-the-architecture-of-nodes-of-ranvier-as-well-as-learning-and-memory
#7
Fucheng Luo, Jessie Zhang, Kathryn Burke, Rita R Romito-DiGiacomo, Robert H Miller, Yan Yang
Myelination of the central nervous system is important for normal motor and sensory neuronal function and recent studies also link it to efficient learning and memory. Cyclin-dependent kinase 5 (Cdk5) is required for normal oligodendrocyte development, myelination and myelin repair. Here we show that conditional deletion of Cdk5 by targeting with CNP (CNP;Cdk5 CKO) results in hypomyelination and disruption of the structural integrity of Nodes of Ranvier. In addition, CNP;Cdk5 CKO mice exhibited a severe impairment of learning and memory compared to controls that may reflect perturbed neuron-glial interactions...
May 2, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29679417/a-probiotic-modulates-the-microbiome-and-immunity-in-multiple-sclerosis
#8
Stephanie K Tankou, Keren Regev, Brian C Healy, Emily Tjon, Luca Laghi, Laura M Cox, Pia Kivisäkk, Isabelle V Pierre, Hrishikesh Lokhande, Roopali Gandhi, Sandra Cook, Bonnie Glanz, James Stankiewicz, Howard L Weiner
OBJECTIVE: Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: MS patients (N=9) and controls (N=13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium and Streptococcus twice daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2-month treatment, and 3 months after discontinuation of therapy...
April 20, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29661806/daclizumab-therapy-for-multiple-sclerosis
#9
Bibiana Bielekova
Daclizumab is a humanized monoclonal antibody that prevents formation of high-affinity interleukin (IL)-2 receptor (IL-2R). Because activated T cells up-regulate high-affinity IL-2R and IL-2 is used to grow activated T cells in vitro, daclizumab was envisioned to selectively inhibit activated T cells. However, the mechanism of action (MOA) of daclizumab is surprisingly broad and it includes many unanticipated effects on innate immunity. Specifically, daclizumab modulates the development of innate lymphoid cells, leading to expansion of immunoregulatory CD56bright natural killer (NK) cells...
April 16, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29619030/dopaminergic-stimulation-of-myeloid-antigen-presenting-cells-attenuates-signal-transducer-and-activator-of-transcription-3-activation-favouring-the-development-of-experimental-autoimmune-encephalomyelitis
#10
Carolina Prado, Michela Gaiazzi, Hugo González, Valentina Ugalde, Alicia Figueroa, Francisco J Osorio-Barrios, Ernesto López, Alvaro Lladser, Emanuela Rasini, Franca Marino, Mauro Zaffaroni, Marco Cosentino, Rodrigo Pacheco
The dual potential to promote tolerance or inflammation to self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of dopamine receptor D5 (DRD5) in DCs potentiates their inflammatory behaviour, favouring the development of experimental autoimmune encephalomyelitis (EAE). Here, we aimed to decipher the underlying mechanism and to test its relevance in multiple sclerosis (MS) patients. Our data shows that DRD5-deficiency confined to DCs in EAE mice resulted in reduced frequencies of CD4+ T-cell subsets with inflammatory potential in the central nervous system, including not only Th1 and Th17 cells but also granulocyte-macrophage colony-stimulating factor producers...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29608575/ozanimod-rpc1063-a-selective-s1pr1-and-s1pr5-modulator-reduces-chronic-inflammation-and-alleviates-kidney-pathology-in-murine-systemic-lupus-erythematosus
#11
Kristen R Taylor Meadows, Marcos W Steinberg, Bryan Clemons, Matthew E Stokes, Gregory J Opiteck, Robert Peach, Fiona L Scott
Ozanimod (RPC1063) is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis. Ozanimod and its active metabolite, RP-101075, exhibit a similar specificity profile at the S1P receptor family in vitro and pharmacodynamic profile in vivo. The NZBWF1 mouse model was used in therapeutic dosing mode to assess the potential benefit of ozanimod and RP-101075 in an established animal model of systemic lupus erythematosus...
2018: PloS One
https://www.readbyqxmd.com/read/29572810/chloroquine-treated-dendritic-cells-require-stat1-signaling-for-their-tolerogenic-activity
#12
Rodolfo Thome, Amanda Pires Bonfanti, Javad Rasouli, Elisabeth Rose Mari, Guang-Xian Zhang, Abdolmohamad Rostami, Liana Verinaud
Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are T cell-driven autoimmune diseases of the central nervous system (CNS) where interleukin (IL)-17-producing Th17 cells promote damage and are pathogenic. Conversely, tolerogenic dendritic cells (DCs) induce regulatory T (Treg) cells and suppress Th17 cells. Chloroquine (CQ) suppresses EAE through the modulation of DCs by unknown mechanisms. Here we show that signal transducer and activator of transcription (STAT) 1 is necessary for CQ-induced tolerogenic DCs (tolDCs) to efficiently suppress EAE...
March 23, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29572472/diversity-of-innate-immune-cell-subsets-across-spatial-and-temporal-scales-in-an-eae-mouse-model
#13
Céline Caravagna, Alexandre Jaouën, Sophie Desplat-Jégo, Keith K Fenrich, Elise Bergot, Hervé Luche, Pierre Grenot, Geneviève Rougon, Marie Malissen, Franck Debarbieux
In both multiple sclerosis and its model experimental autoimmune encephalomyelitis (EAE), the extent of resident microglia activation and infiltration of monocyte-derived cells to the CNS is positively correlated to tissue damage. To address the phenotype characterization of different cell subsets, their spatio-temporal distributions and contributions to disease development we induced EAE in Thy1-CFP//LysM-EGFP//CD11c-EYFP reporter mice. We combined high content flow cytometry, immunofluorescence and two-photon imaging in live mice and identified a stepwise program of inflammatory cells accumulation...
March 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29470604/cathepsin-h-deficiency-in-mice-induces-excess-th1-cell-activation-and-early-onset-of-eae-though-impairment-of-toll-like-receptor-3-cascade
#14
Ryo Okada, Xinwen Zhang, Yuka Harada, Zhou Wu, Hiroshi Nakanishi
OBJECTIVE: The objective of this study is to investigate the role of cathepsin H (CatH), a lysosomal cysteine protease, in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. METHODS: EAE was induced in CatH-deficient mice (CatH-/- ) and wild-type littermates (+/+) using myelin oligodendrocyte glycoprotein (MOG) 35-55. The effects of CatH deficiency were determined by clinical scoring, mRNA expression levels of Tbx21, Rorc and FoxP3, protein levels of poly(I:C)-induced toll-like receptor 3 (TLR3) and phosphorylation of IRF3, and secretion of interferon-β (IFN-β) by splenocytes...
May 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29440425/bryostatin-1-alleviates-experimental-multiple-sclerosis
#15
Michael D Kornberg, Matthew D Smith, Hasti Atashi Shirazi, Peter A Calabresi, Solomon H Snyder, Paul M Kim
Multiple sclerosis (MS) is an inflammatory disorder targeting the central nervous system (CNS). The relapsing-remitting phase of MS is largely driven by peripheral activation of autoreactive T-helper (Th) 1 and Th17 lymphocytes. In contrast, compartmentalized inflammation within the CNS, including diffuse activation of innate myeloid cells, characterizes the progressive phase of MS, the most debilitating phase that currently lacks satisfactory treatments. Recently, bryostatin-1 (bryo-1), a naturally occurring, CNS-permeable compound with a favorable safety profile in humans, has been shown to act on antigen-presenting cells to promote differentiation of lymphocytes into Th2 cells, an action that might benefit Th1-driven inflammatory conditions such as MS...
February 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29426702/high-dimensional-single-cell-mapping-of-central-nervous-system-immune-cells-reveals-distinct-myeloid-subsets-in-health-aging-and-disease
#16
Dunja Mrdjen, Anto Pavlovic, Felix J Hartmann, Bettina Schreiner, Sebastian G Utz, Brian P Leung, Iva Lelios, Frank L Heppner, Jonathan Kipnis, Doron Merkler, Melanie Greter, Burkhard Becher
Individual reports suggest that the central nervous system (CNS) contains multiple immune cell types with diverse roles in tissue homeostasis, immune defense, and neurological diseases. It has been challenging to map leukocytes across the entire brain, and in particular in pathology, where phenotypic changes and influx of blood-derived cells prevent a clear distinction between reactive leukocyte populations. Here, we applied high-dimensional single-cell mass and fluorescence cytometry, in parallel with genetic fate mapping systems, to identify, locate, and characterize multiple distinct immune populations within the mammalian CNS...
February 20, 2018: Immunity
https://www.readbyqxmd.com/read/29394220/beneficial-effect-of-atorvastatin-modified-dendritic-cells-pulsed-with-myelin-oligodendrocyte-glycoprotein-autoantigen-on-experimental-autoimmune-encephalomyelitis
#17
Zhibo Chen, Dehao Yang, Xiao Peng, Jie Lin, Zhongqian Su, Jia Li, Xu Zhang, Yiyun Weng
It is well known that dendritic cells play a key role in producing antigen-specific responses. Inversely, tolerogenic dendritic cells (TolDCs), a specialized subset, induce immune tolerance and negatively regulate autoimmune responses. Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the mevalonate pathway for cholesterol biosynthesis, might be a promising inductive agent for inducing TolDCs. This study aimed to investigate the effectiveness of TolDCs induced by atorvastatin pulsed with myelin oligodendrocyte glycoprotein 35-55 peptide (MOG35-55) in experimental autoimmune encephalomyelitis mice established by MOG35-55 immunization and to investigate the potential effects on Th17/Treg balance in the murine model of multiple sclerosis...
March 7, 2018: Neuroreport
https://www.readbyqxmd.com/read/29368985/noncanonical-autophagy-in-dendritic-cells-triggers-cns-autoimmunity
#18
Christian W Keller, Jan D Lünemann
Reactivation and expansion of myelin-reactive CD4+ T cells within the central nervous system (CNS) are considered to play a key role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). We demonstrated that accumulation of myelin-specific CD4+ T cells within the CNS and subsequent clinical disease development require autophagy related (ATG) protein-dependent phagocytosis in dendritic cells (DCs). Genetic ablation of this pathway impairs presentation of myelin-associated antigen following phagocytosis of injured, phosphatidylserine-exposing oligodendroglial cells...
January 25, 2018: Autophagy
https://www.readbyqxmd.com/read/29342287/to-the-brain-and-back-migratory-paths-of-dendritic-cells-in-multiple-sclerosis
#19
Maxime De Laere, Zwi N Berneman, Nathalie Cools
Migration of dendritic cells (DC) to the central nervous system (CNS) is a critical event in the pathogenesis of multiple sclerosis (MS). While up until now, research has mainly focused on the transmigration of DC through the blood-brain barrier, experimental evidence points out that also the choroid plexus and meningeal vessels represent important gateways to the CNS, especially in early disease stages. On the other hand, DC can exit the CNS to maintain immunological tolerance to patterns expressed in the CNS, a process that is perturbed in MS...
January 12, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29330324/betaine-ameliorates-experimental-autoimmune-encephalomyelitis-by-inhibiting-dendritic-cell-derived-il-6-production-and-th17-differentiation
#20
Cuixia Yang, Weiming Lai, Jinfeng Zhou, Xinyuan Zheng, Yingying Cai, Wanjie Yang, Sirong Xie, Yuan Gao, Changsheng Du
IL-17-secreting T cells (Th17 cells) play a pathogenic role in multiple autoimmune diseases, including multiple sclerosis (MS), and dendritic cell (DC)-derived cytokines play pivotal roles in promoting the differentiation of naive CD4+ T cells into Th cell subsets (Th1 and Th17). Therefore, small molecules blocking the key cytokines produced by DCs will be beneficial in MS. In this article, we report that betaine treatment ameliorates MS pathogenesis by inhibiting DC-derived IL-6 production and Th17 differentiation...
February 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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