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multiple sclerosis and dendritic cells

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https://www.readbyqxmd.com/read/28926402/reversing-hiv-latency-via-sphingosine-1-phosphate-receptor-1-signaling
#1
Charline Duquenne, Sandrine Gimenez, Adeline Guigues, Benjamin Viala, Caroline Boulouis, Clément Mettling, Damien Maurel, Noëlie Campos, Etienne Doumazane, Laetitia Comps-Agrar, Jamal Tazi, Laurent Prézeau, Pierre Corbeau, Vincent François
OBJECTIVE: In this study, we looked for a new family of latency reversing agents. DESIGN: We searched for G protein-coupled receptors (GPCR) coexpressed with CCR5 in primary CD4+ T cells that activate infected cells and boost HIV production. METHODS: GPCR coexpression was unveiled by RT-PCR. We used FRET to analyze the dimerization with CCR5 of the expressed GPCR. Viral entry was measured by flow cytometry, reverse transcription by quantitative PCR, NFkB translocation by immunofluorescence, LTR activation using a gene reporter assay, and viral production by p24 quantification...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28906131/effects-of-immunomodulators-on-the-response-induced-by-vaccines-against-autoimmune-diseases
#2
Dante J Marciani
A promising treatment for T-cell-mediated autoimmune diseases is the induction of immune tolerance by modulating the immune response against self-antigens, an objective that may be achieved by vaccination. There are two main types of vaccines currently under development. The tolerogenic vaccines, composed of proteins formed by a cytokine fused to a self-antigen, which usually induce tolerance by eliminating the T-cells that are immune reactive against the self-antigen. The immunogenic vaccines, comprised of a self-antigen plus a sole Th2 adjuvant either free or conjugated, that alleviate autoimmunity by switching the immune response against the self-antigen, from a damaging pro-inflammatory Th1/Th17 to an anti-inflammatory Th2 immunity...
September 14, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28859672/safety-and-in-vivo-immune-assessment-of-escalating-doses-of-oral-laquinimod-in-patients-with-rrms
#3
Tjalf Ziemssen, Hayrettin Tumani, Tony Sehr, Katja Thomas, Friedemann Paul, Nils Richter, Emil Samara, Ofer Spiegelstein, Ella Sorani, Oren Bar-Ilan, Dorit Mimrod, Liat Hayardeny
BACKGROUND: Laquinimod is an oral immunomodulator in clinical development to treat relapsing-remitting multiple sclerosis (RRMS). Laquinimod is in clinical development for the treatment of multiple sclerosis and Huntington Disease (HD). The objective of this study is to assess the safety, tolerability, pharmacokinetics (PK) and cytoimmunologic effects following escalating doses of laquinimod in patients with RRMS. METHODS: One hundred twelve patients were randomly assigned to laquinimod/placebo in a series of separate dose-escalating cohorts starting from a daily oral dose of 0...
August 31, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28851867/a-unique-tolerizing-dendritic-cell-phenotype-induced-by-the-synthetic-triterpenoid-cddo-dfpa-rta-408-is-protective-against-eae
#4
Hsi-Ju Wei, Tej K Pareek, Qi Liu, John J Letterio
Tolerogenic dendritic cells (DCs) have emerged as relevant clinical targets for the treatment of multiple sclerosis and other autoimmune disorders. However, the pathways essential for conferring the tolerizing DC phenotype and optimal methods for their induction remain an intense area of research. Triterpenoids are a class of small molecules with potent immunomodulatory activity linked to activation of Nrf2 target genes, and can also suppress the manifestations of experimental autoimmune encephalomyelitis (EAE)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844606/ampk-activation-role-in-the-signaling-pathways-of-neuroinflammation-and-neurodegeneration
#5
REVIEW
Christina Alves Peixoto, Wilma Helena de Oliveira, Shyrlene Meiry da Racho Araújo, Ana Karolina Santana Nunes
Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionarily conserved sensor of cellular energy status and has been reported to be involved in chronic inflammatory disorders. AMPK is expressed in immune cells, such as dendritic cells, macrophages, lymphocytes and neutrophils, and is an important regulator of inflammatory responses through the regulation of complex signaling networks in part by inhibiting downstream cascade pathways, such as nuclear factor kB, which is a key regulator of innate immunity and inflammation, as well as acting as a negative regulator of toll-like receptors...
August 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28803660/multiple-sclerosis-skin-induced-antigen-specific-immune-tolerance
#6
REVIEW
Paula Wildner, Krzysztof W Selmaj
Multiple sclerosis (MS) is a highly prevalent demyelinating disorder, presumed to be driven by an autoimmune response toward the central nervous system (CNS) components. All currently available treatments modulate the immune system globally and besides the reduction of disease activity, they may also impose considerable disturbances on the immune protective mechanisms. Thus, induction of antigen-specific immune tolerance remains the ultimate goal of MS therapy. Such approach carries promising therapeutic perspectives and, above all, a desirable safety profile...
August 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28793252/human-gut-derived-commensal-bacteria-suppress-cns-inflammatory-and-demyelinating-disease
#7
Ashutosh Mangalam, Shailesh K Shahi, David Luckey, Melissa Karau, Eric Marietta, Ningling Luo, Rok Seon Choung, Josephine Ju, Ramakrishna Sompallae, Katherine Gibson-Corley, Robin Patel, Moses Rodriguez, Chella David, Veena Taneja, Joseph Murray
The human gut is colonized by a large number of microorganisms (∼10(13) bacteria) that support various physiologic functions. A perturbation in the healthy gut microbiome might lead to the development of inflammatory diseases, such as multiple sclerosis (MS). Therefore, gut commensals might provide promising therapeutic options for treating MS and other diseases. We report the identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28772190/an-antigen-specific-semi-therapeutic-treatment-with-local-delivery-of-tolerogenic-factors-through-a-dual-sized-microparticle-system-blocks-experimental-autoimmune-encephalomyelitis
#8
Jonathan J Cho, Joshua M Stewart, Theodore T Drashansky, Maigan A Brusko, Ashley N Zuniga, Kyle J Lorentsen, Benjamin G Keselowsky, Dorina Avram
Antigen-specific treatments are highly desirable for autoimmune diseases in contrast to treatments which induce systemic immunosuppression. A novel antigen-specific therapy has been developed which, when administered semi-therapeutically, is highly efficacious in the treatment of the mouse model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). The treatment uses dual-sized, polymeric microparticles (dMPs) loaded with specific antigen and tolerizing factors for intra- and extra-cellular delivery, designed to recruit and modulate dendritic cells toward a tolerogenic phenotype without systemic release...
July 24, 2017: Biomaterials
https://www.readbyqxmd.com/read/28732748/controlling-the-pro-inflammatory-function-of-6-sulfo-lacnac-slan-dendritic-cells-with-dimethylfumarate
#9
Stephanie Oehrl, Florina Olaru, Anja Kunze, Michael Maas, Silvia Pezer, Marc Schmitz, Knut Schäkel
BACKROUND: The fumaric acid ester (FAE) dimethylfumarate (DMF) is a small molecule immunomodulator successfully used for the treatment of psoriasis and multiple sclerosis (MS). DMF is thought to inhibit pathogenic immune responses with Th17/Th1T cells, and IL-23/IL-12 producing dendritic cells (DCs). 6-sulfo LacNAc expressing dendritic cells (slanDCs) are a human pro-inflammatory cell type found frequently among the infiltrating leukocytes in skin lesions of psoriasis and brain lesions of MS...
June 24, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28729867/exposure-to-the-epstein-barr-viral-antigen-latent-membrane-protein-1-induces-myelin-reactive-antibodies-in-vivo
#10
Yakov Lomakin, Georgii Pavlovich Arapidi, Alexander Chernov, Rustam Ziganshin, Evgenii Tcyganov, Irina Lyadova, Ivan Olegovich Butenko, Maria Osetrova, Natalia Ponomarenko, Georgy Telegin, Vadim Markovich Govorun, Alexander Gabibov, Alexey Belogurov
Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP)-specific antibodies from MS patients cross-react with Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1). In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28681930/synthesis-and-biological-evaluation-of-ionizable-lipid-materials-for-the-in-vivo-delivery-of-messenger-rna-to-b-lymphocytes
#11
Owen S Fenton, Kevin J Kauffman, James C Kaczmarek, Rebecca L McClellan, Siddharth Jhunjhunwala, Mark W Tibbitt, Manhao D Zeng, Eric A Appel, Joseph R Dorkin, Faryal F Mir, Jung H Yang, Matthias A Oberli, Michael W Heartlein, Frank DeRosa, Robert Langer, Daniel G Anderson
B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T-cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and cancers such as multiple sclerosis and non-Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose-dependent and time-controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells...
September 2017: Advanced Materials
https://www.readbyqxmd.com/read/28646573/interferon-%C3%AE-regulates-dendritic-cell-activation-and-migration-in-experimental-autoimmune-encephalomyelitis
#12
Leesa M Pennell, Eleanor N Fish
CD11c+ dendritic cells (DCs) exert a critical role as antigen-presenting cells in regulating pathogenic T cells in multiple sclerosis (MS). To determine whether the therapeutic benefit of interferon (IFN)-β treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN-β(+/+) and IFN-β(-/-) mice using a myelin oligodendrocyte glycoprotein (MOG) peptide-induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our earlier work identified that IFN-β(-/-) mice exhibit earlier onset and more rapid progression of neurologic impairment compared with IFN-β(+/+) mice...
June 24, 2017: Immunology
https://www.readbyqxmd.com/read/28646511/control-of-autoimmune-inflammation-using-liposomes-to-deliver-positive-allosteric-modulators-of-metabotropic-glutamate-receptors
#13
Joshua M Gammon, Arjun R Adapa, Christopher M Jewell
Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation...
June 24, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28617989/1-25-dihydroxyvitamin-d3-induced-dendritic-cells-suppress-experimental-autoimmune-encephalomyelitis-by-increasing-proportions-of-the-regulatory-lymphocytes-and-reducing-th1-th17-cells
#14
Zhongxiang Xie, Jingtao Chen, Chao Zheng, Jing Wu, Yun Cheng, Shan Zhu, Chenhong Lin, Qingqing Cao, Jie Zhu, Tao Jin
Dendritic cells (DCs), a bridge of innate and adaptive immune responses, play a key role in the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Administration of tolerogenic DCs has been used as an immunotherapy in the autoimmune diseases. Deficiency of vitamin D is an environmental risk factor of MS. In this study, we induced tolerogenic DCs by 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) and adoptive transferred the tolerogenic DCs (VD3-DCs) into EAE mice...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28617358/-dendritic-cells-in-multiple-sclerosis
#15
M V Melnikov, M V Paschenkov, A N Boyko
Main functions, structure and stages of development of dendritic cells (DCs) are reviewed. A role of DCs in the development of immune tolerance and autoimmune diseases as well as involvement of DCs in the immunopathogenesis of multiple sclerosis (MS and their therapeutic potential in the treatment of MS are discussed.
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28617321/evolving-identification-of-blood-cells-associated-with-clinically-isolated-syndrome-importance-of-time-since-clinical-presentation-and-diagnostic-mri
#16
Stephanie Trend, Anderson P Jones, Sian Geldenhuys, Scott N Byrne, Marzena J Fabis-Pedrini, David Nolan, David R Booth, William M Carroll, Robyn M Lucas, Allan G Kermode, Prue H Hart
It is not clear how the profile of immune cells in peripheral blood differs between patients with clinically isolated syndrome (CIS) and healthy controls (HC). This study aimed to identify a CIS peripheral blood signature that may provide clues for potential immunomodulatory approaches early in disease. Peripheral blood mononuclear cells (PBMCs) were collected from 18 people with CIS, 19 HC and 13 individuals with other demyelinating conditions (ODC) including multiple sclerosis (MS). Individuals with CIS separated into two groups, namely those with early (≤14 days post-diagnostic magnetic resonance imaging (MRI); n = 6) and late (≥27 days; n = 12) blood sampling...
June 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28593827/liposome-based-immunotherapy-against-autoimmune-diseases-therapeutic-effect-on-multiple-sclerosis
#17
Irma Pujol-Autonell, Maria-Jose Mansilla, Silvia Rodriguez-Fernandez, Mary Cano-Sarabia, Juan Navarro-Barriuso, Rosa-Maria Ampudia, Aleix Rius, Sonia Garcia-Jimeno, David Perna-Barrull, Eva Martinez-Caceres, Daniel Maspoch, Marta Vives-Pi
AIM: Based on the ability of apoptosis to induce immunological tolerance, liposomes were generated mimicking apoptotic cells, and they arrest autoimmunity in Type 1 diabetes. Our aim was to validate the immunotherapy in other autoimmune disease: multiple sclerosis. MATERIALS & METHODS: Phosphatidylserine-rich liposomes were loaded with disease-specific autoantigen. Therapeutic capability of liposomes was assessed in vitro and in vivo. RESULTS: Liposomes induced a tolerogenic phenotype in dendritic cells, and arrested autoimmunity, thus decreasing the incidence, delaying the onset and reducing the severity of experimental disease, correlating with an increase in a probably regulatory CD25(+) FoxP3(-) CD4(+) T-cell subset...
June 2017: Nanomedicine
https://www.readbyqxmd.com/read/28588487/gyf-21-an-epoxide-2-2-phenethyl-chromone-derivative-suppresses-innate-and-adaptive-immunity-via-inhibiting-stat1-3-and-nf-%C3%AE%C2%BAb-signaling-pathways
#18
Ran Guo, Yun-Fang Zhao, Jun Li, Yu-Fan Gu, Hui-Xia Huo, Shan-Shan Li, Yue-Lin Song, Zhi-Xiang Zhu, Peng-Fei Tu
Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system characterized by demyelinating plaques and axonal loss. Inhibition on over activation of innate and adaptive immunity provides a rationale strategy for treatment of multiple sclerosis. In the present study, we investigated the inhibitory effects of GYF-21, an epoxide 2-(2-phenethyl)-chromone derivative isolated from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat multiple sclerosis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28578466/dopaminergic-regulation-of-innate-immunity-a-review
#19
REVIEW
Monica Pinoli, Franca Marino, Marco Cosentino
Dopamine (DA) is a neurotransmitter in the central nervous system as well as in peripheral tissues. Emerging evidence however points to DA also as a key transmitter between the nervous system and the immune system as well as a mediator produced and released by immune cells themselves. Dopaminergic pathways have received so far extensive attention in the adaptive branch of the immune system, where they play a role in health and disease such as multiple sclerosis, rheumatoid arthritis, cancer, and Parkinson's disease...
June 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28578388/antibody-blockade-of-clec12a-delays-eae-onset-and-attenuates-disease-severity-by-impairing-myeloid-cell-cns-infiltration-and-restoring-positive-immunity
#20
Divya Sagar, Narendra P Singh, Rashida Ginwala, Xiaofang Huang, Ramila Philip, Mitzi Nagarkatti, Prakash Nagarkatti, Konstantin Neumann, Jürgen Ruland, Allison M Andrews, Servio H Ramirez, Zafar K Khan, Pooja Jain
The mechanism of dendritic cells (DCs) recruitment across the blood brain barrier (BBB) during neuroinflammation has been the least explored amongst all leukocytes. For cells of myeloid origin, while integrins function at the level of adhesion, the importance of lectins remains unknown. Here, we identified functions of one C-type lectin receptor, CLEC12A, in facilitating DC binding and transmigration across the BBB in response to CCL2 chemotaxis. To test function of CLEC12A in an animal model of multiple sclerosis (MS), we administered blocking antibody to CLEC12A that significantly ameliorated disease scores in MOG35-55-induced progressive, as well as PLP138-151-induced relapsing-remitting experimental autoimmune encephalomyelitis (EAE) mice...
June 2, 2017: Scientific Reports
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