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multiple sclerosis and dendritic cells

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https://www.readbyqxmd.com/read/29330324/betaine-ameliorates-experimental-autoimmune-encephalomyelitis-by-inhibiting-dendritic-cell-derived-il-6-production-and-th17-differentiation
#1
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...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29302779/glia-to-neuron-transfer-of-mirnas-via-extracellular-vesicles-a-new-mechanism-underlying-inflammation-induced-synaptic-alterations
#2
Ilaria Prada, Martina Gabrielli, Elena Turola, Alessia Iorio, Giulia D'Arrigo, Roberta Parolisi, Mariacristina De Luca, Marco Pacifici, Mattia Bastoni, Marta Lombardi, Giuseppe Legname, Dan Cojoc, Annalisa Buffo, Roberto Furlan, Francesca Peruzzi, Claudia Verderio
Recent evidence indicates synaptic dysfunction as an early mechanism affected in neuroinflammatory diseases, such as multiple sclerosis, which are characterized by chronic microglia activation. However, the mode(s) of action of reactive microglia in causing synaptic defects are not fully understood. In this study, we show that inflammatory microglia produce extracellular vesicles (EVs) which are enriched in a set of miRNAs that regulate the expression of key synaptic proteins. Among them, miR-146a-5p, a microglia-specific miRNA not present in hippocampal neurons, controls the expression of presynaptic synaptotagmin1 (Syt1) and postsynaptic neuroligin1 (Nlg1), an adhesion protein which play a crucial role in dendritic spine formation and synaptic stability...
January 4, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29288202/gm-csf-promotes-chronic-disability-in-experimental-autoimmune-encephalomyelitis-by-altering-the-composition-of-central-nervous-system-infiltrating-cells-but-is-dispensable-for-disease-induction
#3
Patrick C Duncker, Joshua S Stoolman, Amanda K Huber, Benjamin M Segal
GM-CSF has been portrayed as a critical cytokine in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and, ostensibly, in multiple sclerosis. C57BL/6 mice deficient in GM-CSF are resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 The mechanism of action of GM-CSF in EAE is poorly understood. In this study, we show that GM-CSF augments the accumulation of MOG35-55-specific T cells in the skin draining lymph nodes of primed mice, but it is not required for the development of encephalitogenic T cells...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29283442/myeloid-cell-plasticity-in-the-evolution-of-central-nervous-system-autoimmunity
#4
David A Giles, Jesse M Washnock-Schmid, Patrick C Duncker, Somiah Dahlawi, Gerald Ponath, David Pitt, Benjamin M Segal
OBJECTIVE: Myeloid cells, including macrophages and dendritic cells, are a prominent component of central nervous system (CNS) infiltrates during multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE). Although myeloid cells are generally thought to be pro-inflammatory, alternatively-polarized subsets can serve non-inflammatory and/or reparative functions. Here we investigate the heterogeneity and biological properties of myeloid cells during central nervous system autoimmunity...
December 28, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29250057/update-on-dendritic-cell-induced-immunological-and-clinical-tolerance
#5
REVIEW
Carolina Obregon, Rajesh Kumar, Manuel Antonio Pascual, Giuseppe Vassalli, Déla Golshayan
Dendritic cells (DCs) as highly efficient antigen-presenting cells are at the interface of innate and adaptive immunity. As such, they are key mediators of immunity and antigen-specific immune tolerance. Due to their functional specialization, research efforts have focused on the characterization of DCs subsets involved in the initiation of immunogenic responses and in the maintenance of tissue homeostasis. Tolerogenic DCs (tolDCs)-based therapies have been designed as promising strategies to prevent and control autoimmune diseases as well as allograft rejection after solid organ transplantation (SOT)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29238348/the-mannose-receptor-in-regulation-of-helminth-mediated-host-immunity
#6
REVIEW
Irma van Die, Richard D Cummings
Infection with parasitic helminths affects humanity and animal welfare. Parasitic helminths have the capacity to modulate host immune responses to promote their survival in infected hosts, often for a long time leading to chronic infections. In contrast to many infectious microbes, however, the helminths are able to induce immune responses that show positive bystander effects such as the protection to several immune disorders, including multiple sclerosis, inflammatory bowel disease, and allergies. They generally promote the generation of a tolerogenic immune microenvironment including the induction of type 2 (Th2) responses and a sub-population of alternatively activated macrophages...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29233943/atg-dependent-phagocytosis-in-dendritic-cells-drives-myelin-specific-cd4-t-cell-pathogenicity-during-cns-inflammation
#7
Christian W Keller, Christina Sina, Monika B Kotur, Giulia Ramelli, Sarah Mundt, Isaak Quast, Laure-Anne Ligeon, Patrick Weber, Burkhard Becher, Christian Münz, Jan D Lünemann
Although reactivation and accumulation of autoreactive CD4+ T cells within the CNS are considered to play a key role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), the mechanisms of how these cells recognize their target organ and induce sustained inflammation are incompletely understood. Here, we report that mice with conditional deletion of the essential autophagy protein ATG5 in classical dendritic cells (DCs), which are present at low frequencies in the nondiseased CNS, are completely resistant to EAE development following adoptive transfer of myelin-specific T cells and show substantially reduced in situ CD4+ T cell accumulation during the effector phase of the disease...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29228214/oestrogen-receptor-%C3%AE-ligand-acts-on-cd11c-cells-to-mediate-protection-in-experimental-autoimmune-encephalomyelitis
#8
Roy Y Kim, Darian Mangu, Alexandria S Hoffman, Rojan Kovash, Eunice Jung, Noriko Itoh, Rhonda Voskuhl
Oestrogen treatments are neuroprotective in a variety of neurodegenerative disease models. Selective oestrogen receptor modifiers are needed to optimize beneficial effects while minimizing adverse effects to achieve neuroprotection in chronic diseases. Oestrogen receptor beta (ERβ) ligands are potential candidates. In the multiple sclerosis model chronic experimental autoimmune encephalomyelitis, ERβ-ligand treatment is neuroprotective, but mechanisms underlying this neuroprotection remain unclear. Specifically, whether there are direct effects of ERβ-ligand on CD11c+ microglia, myeloid dendritic cells or macrophages in vivo during disease is unknown...
December 8, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29213032/-staging-of-neuroplasticity-alterations-during-epileptogenesis-temporal-lobe-epileply-as-an-example
#9
N V Gulyaeva
Using temporal lobe epilepsy as an example, staging of long term plasticity in the hippocampus is considered. Major stages demonstrating opposite alterations in neuroplasticity are active epileptogenesis and the period of established temporal lobe epilepsy. During the epileptogenesis, multiple events resulting in forming of epileptic neuronal nets occur: changes in glutamatergic and GABAergic neurons, increase of aberrant neurogenesis, axonal sprouting and dendrite remodeling, particularly, supported by an excessive enhancement of the BDNF system in specific hippocampal regions...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29201154/lymphatic-system-and-gut-microbiota-affect-immunopathology-of-neuroinflammatory-diseases-including-multiple-sclerosis-neuromyelitis-optica-and-alzheimer-s-disease
#10
Ikuo Tsunoda
Microbial infections lead to neurological damages either by direct infection in the nervous tissues or by uncontrolled immune responses (immunopathology). For example, in Zika virus infection, microcephaly can be caused by the former, i.e., direct viral infection in the brain, while Guillain-Barré syndrome (GBS) seems to be antibody-mediated immunopathology. Although a variety of factors affect immunopathology, two essential systems maintaining whole-body homeostasis had long been neglected: 1) the lymphatic system and 2) microbiota...
August 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/29163476/induction-of-peripheral-tolerance-in-ongoing-autoimmune-inflammation-requires-interleukin-27-signaling-in-dendritic-cells
#11
Rodolfo Thomé, Jason N Moore, Elisabeth R Mari, Javad Rasouli, Daniel Hwang, Satoshi Yoshimura, Bogoljub Ciric, Guang-Xian Zhang, Abdolmohamad M Rostami
Peripheral tolerance to autoantigens is induced via suppression of self-reactive lymphocytes, stimulation of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Interleukin (IL)-27 induces tolerogenic DCs and Treg cells; however, it is not known whether IL-27 is important for tolerance induction. We immunized wild-type (WT) and IL-27 receptor (WSX-1) knockout mice with MOG35-55 for induction of experimental autoimmune encephalomyelitis and intravenously (i.v.) injected them with MOG35-55 after onset of disease to induce i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29148731/conjugation-of-transforming-growth-factor-beta-to-antigen-loaded-poly-lactide-co-glycolide-nanoparticles-enhances-efficiency-of-antigen-specific-tolerance
#12
Liam M Casey, Ryan M Pearson, Kevin Hughes, Jeffrey Liu, Justin Rose, Madeleine G North, Leon Wang, Lei Mei, Stephen D Miller, Lonnie D Shea
Current strategies for treating autoimmunity involve the administration of broad-acting immunosuppressive agents that impair healthy immunity. Intravenous (i.v.) administration of poly(lactide-co-glycolide) nanoparticles (NPs) containing disease-relevant antigens (Ag-NPs) have demonstrated antigen(Ag)-specific immune tolerance in models of autoimmunity. However, subcutaneous (s.c.) delivery of Ag-NPs has not been effective. This investigation tested the hypothesis that co-delivery of the immunomodulatory cytokine, transforming growth factor beta 1 (TGF-β), on Ag-NPs would modulate the immune response to Ag-NPs and improve the efficiency of tolerance induction...
November 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29106333/monomethyl-fumarate-treatment-impairs-maturation-of-human-myeloid-dendritic-cells-and-their-ability-to-activate-t-cells
#13
Maria Antonietta Mazzola, Radhika Raheja, Keren Regev, Vanessa Beynon, Felipe von Glehn, Anu Paul, Isabelle Pierre, Pia Kivisakk, Howard L Weiner, Roopali Gandhi
BACKGROUND: Dimethyl fumarate (DMF) and its active metabolite monomethyl fumarate (MMF) effectively lead to reduction in disease relapses and active magnetic resonance imaging (MRI) lesions. DMF and MMF are known to be effective in modulating T- and B-cell responses; however, their effect on the phenotype and function of human myeloid dendritic cells (mDCs) is not fully understood. OBJECTIVE: To investigate the role of MMF on human mDCs maturation and function. METHODS: mDCs from healthy controls were isolated and cultured in vitro with MMF...
November 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29099057/the-c-c-chemokines-ccl17-and-ccl22-and-their-receptor-ccr4-in-cns-autoimmunity
#14
REVIEW
Stefanie Scheu, Shafaqat Ali, Christina Ruland, Volker Arolt, Judith Alferink
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). It affects more than two million people worldwide, mainly young adults, and may lead to progressive neurological disability. Chemokines and their receptors have been shown to play critical roles in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine disease model induced by active immunization with myelin proteins or transfer of encephalitogenic CD4⁺ T cells that recapitulates clinical and neuropathological features of MS...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29075262/clinical-tolerogenic-dendritic-cells-exploring-therapeutic-impact-on-human-autoimmune-disease
#15
REVIEW
Brett Eugene Phillips, Yesica Garciafigueroa, Massimo Trucco, Nick Giannoukakis
Tolerogenic dendritic cell (tDC)-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat autoimmune diseases of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis (MS), and Crohn's disease. This review will address tDC employed in current clinical trials, focusing on cell characteristics, mechanisms of action, and clinical findings. To date, the publicly reported human trials using tDC indicate that regulatory lymphocytes (largely Foxp3+ T-regulatory cell and, in one trial, B-regulatory cells) are, for the most part, increased in frequency in the circulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29074827/-update-on-recent-progress-in-vitamin-d-research-the-effects-of-vitamin-d-in-autoinflammatory-diseases
#16
Tomoka Ao, Junichi Kikuta, Masaru Ishii
Various kinds of immune cells -including dendritic cells, macrophages, T cells and B cells- express the vitamin D receptor and 1α-hydroxylase(CYP27B1). In vitro studies have shown the anti-inflammatory effect of 1,25-dihydroxyvitamin D:the active form of vitamin D. As vitamin D deficiency spread in our society, epidemiological studies have established the association between vitamin D deficiency and incidence or progression of several inflammatory diseases, including rheumatoid arthritis(RA), systemic lupus erythematosus(SLE), and multiple sclerosis(MS)...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/29066789/identification-of-14-dehydroergosterol-as-a-novel-anti-inflammatory-compound-inducing-tolerogenic-dendritic-cells
#17
Yasuhisa Ano, Kumiko Ikado, Kazutoshi Shindo, Hideki Koizumi, Daisuke Fujiwara
Tolerogenic dendritic cells (DCs) have the ability to induce regulatory T cells and play an important role in preventing chronic inflammatory and autoimmune diseases. We have identified a novel compound, 14-dehydroergosterol, from Koji, a Japanese traditional food material fermented with fungi. 14-dehydroergosterol is an ergosterol analogue with a conjugated double bond, but the activity of 14-dehydroergosterol is much higher than that of ergosterol. 14-dehydroergosterol induces the conversion of murine bone marrow (BM)-derived DCs and differentiated DCs into tolerogenic DCs, in which the production of IL-12 is suppressed and that of IL-10 is increased...
October 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29061767/thymic-specific-serine-protease-limits-central-tolerance-and-exacerbates-experimental-autoimmune-encephalomyelitis
#18
Laurent Serre, Maeva Girard, Abdoulraouf Ramadan, Paul Menut, Nelly Rouquié, Liliana E Lucca, Karim Mahiddine, Bertrand Leobon, Lennart T Mars, Sylvie Guerder
The genetic predisposition to multiple sclerosis (MS) is most strongly conveyed by MHC class II haplotypes, possibly by shaping the autoimmune CD4 T cell repertoire. Whether Ag-processing enzymes contribute to MS susceptibility by editing the peptide repertoire presented by these MHC haplotypes is unclear. Thymus-specific serine protease (TSSP) is expressed by thymic epithelial cells and thymic dendritic cells (DCs) and, in these two stromal compartments, TSSP edits the peptide repertoire presented by class II molecules...
October 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29053798/in-vivo-characterization-of-cortical-and-white-matter-neuroaxonal-pathology-in-early-multiple-sclerosis
#19
Tobias Granberg, Qiuyun Fan, Constantina Andrada Treaba, Russell Ouellette, Elena Herranz, Gabriel Mangeat, Céline Louapre, Julien Cohen-Adad, Eric C Klawiter, Jacob A Sloane, Caterina Mainero
Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability...
November 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28966663/alemtuzumab-in-the-long-term-treatment-of-relapsing-remitting-multiple-sclerosis-an-update-on-the-clinical-trial-evidence-and-data-from-the-real-world
#20
Tjalf Ziemssen, Katja Thomas
Alemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS), given as two annual courses on five consecutive days at baseline and on three consecutive days 12 months later. Here we provide an update on the long-term efficacy and safety of alemtuzumab in RRMS, including real-world experience, and advances in our understanding of its mechanism of action. Recent data from the phase II/III extension study have demonstrated that alemtuzumab reduces relapse rates, disability worsening, and the rate of brain volume loss over the long term, with many patients achieving no evidence of disease activity...
October 2017: Therapeutic Advances in Neurological Disorders
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