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multiple sclerosis and dendritic cells

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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
#1
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...
July 6, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28646573/interferon-%C3%AE-regulates-dendritic-cell-activation-and-migration-in-experimental-autoimmune-encephalomyelitis
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28570722/use-of-corneal-confocal-microscopy-to-detect-corneal-nerve-loss-and-increased-dendritic-cells-in-patients-with-multiple-sclerosis
#11
Gulfidan Bitirgen, Zehra Akpinar, Rayaz A Malik, Ahmet Ozkagnici
Importance: Multiple sclerosis (MS) is characterized by demyelination, axonal degeneration, and inflammation. Corneal confocal microscopy has been used to identify axonal degeneration in several peripheral neuropathies. Objective: To assess corneal subbasal nerve plexus morphologic features, corneal dendritic cell (DC) density, and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with MS. Design, Setting, and Participants: This single-center, cross-sectional comparative study was conducted at a tertiary referral university hospital between May 27, 2016, and January 30, 2017...
July 1, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28536579/peripherally-induced-regulatory-t-cells-recruited-protectors-of-the-central-nervous-system-against-autoimmune-neuroinflammation
#12
REVIEW
Andrew Jones, Daniel Hawiger
Defects in regulatory T cells (Treg cells) aggravate multiple sclerosis (MS) after its onset and the absence of Treg cell functions can also exacerbate the course of disease in an animal model of MS. However, autoimmune neuroinflammation in many MS models can be acutely provoked in healthy animals leading to an activation of encephalitogenic T cells despite the induction of immune tolerance in the thymus including thymically produced (t)Treg cells. In contrast, neuroinflammation can be ameliorated or even completely prevented by the antigen-specific Treg cells formed extrathymically in the peripheral immune system (pTreg cells) during tolerogenic responses to relevant neuronal antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28466383/photopheresis-advances-and-use-in-systemic-sclerosis
#13
REVIEW
Xiaolong Alan Zhou, Jaehyuk Choi
PURPOSE OF REVIEW: Extracorporeal photochemotherapy (photopheresis, ECP) is a cell-based immunomodulatory treatment that separates leukocytes from peripheral blood, exposes them to a photosensitizing agent followed by ultraviolet A light, and then reinfuses them back into the patient. ECP has been found to be effective for graft versus host disease, transplant rejection, and various autoimmune diseases. The mechanism is not well understood but studies have shown clinical benefit in the treatment of systemic sclerosis (SSc)...
June 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28451557/efficacy-and-safety-of-g2013-as-a-novel-immunosuppressive-agent-on-differentiation-maturation-and-function-of-human-dendritic-cells
#14
Nazanin Arjomand Fard, Nakisa Tabrizian, Reza Mirzaei, Jamshid Hadjati, Farzaneh Tofighi Zavareh, Ali Reza Salehi Nodeh, Abbas Mirshafiey
BACKGROUND: The expanse of dendritic cells (DC) differentiation plays an important role in determining immune response. DC-based immunosuppressive drugs have notable side effects in increasing the risk of infectious diseases and cancers. G2013, as a novel anti-inflammatory and immunosuppressive agent, has been tested in experimental model of multiple sclerosis. The aim of this study was to conduct the safety property of G2013 on dendritic cells biology. METHODS: The effect of G2013 on differentiation, maturation, and function of dendritic cells was examined at Tehran University in 2014...
February 2017: Iranian Journal of Public Health
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
#15
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
#16
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...
June 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
#17
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
#18
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...
July 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
#19
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
#20
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...
July 2017: Journal of Autoimmunity
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