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Ke-Wei Tian, Yuan-Yuan Zhang, Hong Jiang, Shu Han
The placenta has emerged as an attractive source of mesenchymal stem cells (MSCs) because of the absence of ethical issues, non-invasive access, and abundant yield. However, inflammatory cell invasion into grafts negatively impacts the survival and efficacy of transplanted cells. Previous studies have shown that synthetic C16 peptide can competitively block the transmigration of leukocytes into the central nerve system, while angiopoietin-1 (Ang-1) can inhibit inflammation-induced blood vessel leakage and inflammatory cell infiltration in rats with experimental allergic encephalomyelitis (EAE)...
March 15, 2018: Scientific Reports
Zimu Zhang, Zhenyi Xue, Ying Liu, Hongkun Liu, Xiangdong Guo, Yan Li, Hongwei Yang, Lijuan Zhang, Yurong Da, Zhi Yao, Rongxin Zhang
Among T helper (Th) cell subsets differentiated from naive CD4+ T cells, IL-17-producing Th17 cells are closely associated with the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and the MS animal model, experimental autoimmune encephalomyelitis (EAE). The modulation of Th17 differentiation offers a potential avenue for treatment. Although a series of microRNAs (miRNAs) that modulate autoimmune disease development have been reported, further studies on miRNA roles in Th17 differentiation and MS pathogenesis are still warranted...
March 12, 2018: Brain, Behavior, and Immunity
Carmen Scheibenbogen, Madlen Loebel, Helma Freitag, Anne Krueger, Sandra Bauer, Michaela Antelmann, Wolfram Doehner, Nadja Scherbakov, Harald Heidecke, Petra Reinke, Hans-Dieter Volk, Patricia Grabowski
INTRODUCTION: Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) point to an autoimmune disease directed against neurotransmitter receptors. We had observed elevated autoantibodies against ß2 adrenergic receptors, and muscarinic 3 and 4 acetylcholine receptors in a subset of patients. Immunoadsorption (IA) was shown to be effective in removing autoantibodies and improve outcome in various autoimmune diseases...
2018: PloS One
Mohammad Sajad Emami Aleagha, Mohammad Hossein Harirchian, Shahram Lavasani, Mohammad Javan, Abdolamir Allameh
Recently, we reported a positive correlation between Klotho, as an anti-aging protein, and the total antioxidant capacity (TAC) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, there is no information about the Klotho and TAC changes within the central nervous system (CNS). Thus, the current study aimed to employ an experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice using MOG35-55 peptide to examine the relationship between Klotho and TAC within the CNS. To this end, the brain and spinal cord were obtained at the onset and peak stages of EAE as well as non-EAE mice (sham/control groups)...
March 14, 2018: Journal of Molecular Neuroscience: MN
S Bidaran, A R Ahmadi, P Yaghmaei, M H Sanati, A Ebrahim-Habibi
OBJECTIVE: The aim of the present study was to reveal the effect of therapeutic and prophylactic potential of astaxanthin in experimental autoimmune encephalomyelitis (EAE) as an acceptable model for the study of multiple sclerosis (MS). BACKGROUND: Astaxanthin has powerful antioxidant activities as well as several essential biological functions while multiple sclerosis prevention is highly regarded by researchers. METHODS: The astaxanthin potential in prevention of multiple sclerosis was examined in the chronic model of experimental autoimmune encephalomyelitis (EAE) by using female C57BL/6 mice induced with oligodendrocyte glycoprotein (MOG)...
2018: Bratislavské Lekárske Listy
Caroline C Kingdon, Erinna W Bowman, Hayley Curran, Luis Nacul, Eliana M Lacerda
BACKGROUND: People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continue to struggle to have their condition recognised as disabling in the face of public and professional prejudice and discrimination. OBJECTIVE: The aim of this study was to compare the functional status and well-being of people with well-characterised ME/CFS with people with multiple sclerosis (PWMS), as well as healthy controls (HCs). METHODS: In this cross-sectional study, we used data collected as part of the UK ME/CFS Biobank to compare actual participant scores from the Medical Outcomes Survey Short Form-36 v2™ (SF-36v2™) between groups, as a proxy for impact of disability, and from a bespoke questionnaire seeking data on employment and income...
March 13, 2018: PharmacoEconomics Open
James L Quinn, Gaurav Kumar, Agnieshka Agasing, Rose M Ko, Robert C Axtell
Both T cells and B cells are implicated in the pathology of multiple sclerosis (MS), but how these cells cooperate to drive disease remains unclear. Recent studies using experimental autoimmune encephalomyelitis (EAE) demonstrated that the TH17 pathway is correlated with increased numbers of ectopic B-cell follicles in the central nervous system (CNS). As follicular T helper (TFH) cells are regulators of B cell responses, we sought to examine the role of TFH cells in EAE induced by the transfer of myelin-specific TH17 cells (TH17-EAE)...
2018: Frontiers in Immunology
Iris Mair, Stephanie E J Zandee, Iqbal S Toor, Louise Saul, Rhoanne C McPherson, Melanie D Leech, Danielle J Smyth, Richard A O'Connor, Neil C Henderson, Stephen M Anderton
Several inflammatory diseases including multiple sclerosis and inflammatory bowel disease have been associated with dysfunctional and/or reduced numbers of Foxp3+ regulatory T cells (Treg). While numerous mechanisms of action have been discovered by which Treg can exert their function, disease-specific Treg requirements remain largely unknown. We found that the integrin αv, which can pair with several β subunits including β8, is highly upregulated in Treg at sites of inflammation. Using mice that lacked αv expression or β8 expression specifically in Treg, we demonstrate that there was no deficit in Treg accumulation in the central nervous system during experimental autoimmune encephalomyelitis and no difference in the resolution of disease compared to control mice...
2018: Frontiers in Immunology
Elise Allender, Harvinderjeet Deol, Sarah Schram, Kathleen J Maheras, Alexander Gow, Eleanor H Simpson, Fei Song
Neuregulin1 (NRG1) is a differentiation factor that regulates glial development, survival, synaptogenesis, axoglial interactions, and microglial activation. We previously reported that a targeted NRG1 antagonist (HBD-S-H4) given intrathecally, reduces inflammatory microglial activation in a spinal cord pain model and a neurodegenerative disease mouse model in vivo, suggesting that it may have effects in neuroninflammatory and neuronal disorders. We hypothesized that expression of HBD-S-H4 in the central nervous system (CNS) could reduce disease severity in experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS)...
March 10, 2018: Journal of Neuroimmunology
Annie C Bowles, Rachel M Wise, Brittany Y Gerstein, Robert C Thomas, Roberto Ogelman, Regan C Manayan, Bruce A Bunnell
BACKGROUND: The therapeutic efficacy of adipose-derived stem cells (ASCs) has been investigated for numerous clinical indications, including autoimmune and neurodegenerative diseases. Less is known using the crude adipose product called stromal vascular fraction (SVF) as therapy, although our previous studies demonstrated greater efficacy at late-stage disease compared to ASCs in the experimental autoimmune encephalomyelitis (EAE) mouse, a model of multiple sclerosis. In this study, SVF cells and ASCs were administered during the pathogenic progression, designated as early disease, to elucidate immunomodulatory mechanisms when high immune cell activities associated with autoimmune signaling occur...
March 13, 2018: Journal of Neuroinflammation
Peter T Sage, Frank A Schildberg, Raymond A Sobel, Vijay K Kuchroo, Gordon J Freeman, Arlene H Sharpe
The programmed death (PD)-1 coinhibitory receptor regulates the balance between T cell activation and tolerance. Although the PD-1 ligands, PD-L1 and PD-L2, are expressed on a variety of cell types, the cell type-specific functions of PD-1 ligands in inducing signals through PD-1 are unknown. In this study, we use PD-L1 conditional knockout mice to investigate the cell type-specific functions of PD-L1. We demonstrate that PD-L1 expressed on dendritic cells (DCs), and to a lesser extent on B cells, attenuates the progression of experimental autoimmune encephalomyelitis and inhibits naive and effector T cells...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Paul A Smith, Cindy Schmid, Stefan Zurbruegg, Magali Jivkov, Arno Doelemeyer, Diethilde Theil, Valérie Dubost, Nicolau Beckmann
Longitudinal brain atrophy quantification is a critical efficacy measurement in multiple sclerosis (MS) clinical trials and the determination of No Evidence of Disease Activity (NEDA). Utilising fingolimod as a clinically validated therapy we evaluated the use of repeated brain tissue volume measures during chronic experimental autoimmune encephalomyelitis (EAE) as a new preclinical efficacy measure. Brain volume changes were quantified using magnetic resonance imaging (MRI) at 7 Tesla and correlated to treatment-induced brain derived neurotrophic factor (BDNF) measured in blood, cerebrospinal fluid, spinal cord and brain...
March 3, 2018: Journal of Neuroimmunology
Katsuhiro Nakagawa, Takanori Matsuki, Liang Zhao, Kanako Kuniyoshi, Hiroki Tanaka, Isao Ebina, Kenta J Yoshida, Hiroshi Nabeshima, Kiyoharu Fukushima, Hisashi Kanemaru, Fumihiro Yamane, Takahiro Kawasaki, Tomohisa Machida, Hisamichi Naito, Nobuyuki Takakura, Takashi Satoh, Shizuo Akira
Schlafen-8 (Slfn8) is a member of the Schlafen family of proteins, which harbor helicase domains and are induced by LPS and interferons. It has been reported that the Schlafen family are involved in various cellular functions, including proliferation, differentiation and regulation of virus replication. Slfn8 has been implicated in T-cell differentiation in the thymus. However, the roles of Slfn8 in the immune system remains unclear. In this study, we generated Slfn8 knockout mice (Slfn8-/-) and investigated the immunological role of Slfn8 using the T-cell-mediated autoimmune model experimental autoimmune encephalomyelitis (EAE)...
March 8, 2018: International Immunology
Valery I Turobov, Alexey V Danilkovich, Alexei B Shevelev, Yulia K Biryukova, Natalia V Pozdniakova, Viatcheslav N Azev, Arkady N Murashev, Valery M Lipkin, Igor P Udovichenko
Peptide immunocortin sequence corresponds to the amino acid residues 11-20 of the variable part of human immunoglobulin G1 (IgG1) heavy chain. Since immunocortin was shown previously to inhibit phagocytosis in peritoneal macrophages and ConA-induced T-lymphocytes proliferation in culture, we suggested that immunocortin administering may be of use for patients with self-immune syndrome. Immunocortin in concentration 10 μM inhibited proliferation of both antigen (myelin)-induced and ConA-induced LN lymphocytes isolated from the lymph nodes of Dark Agouti (DA) rats immunized with chorda shear...
2018: Frontiers in Pharmacology
Jianghong Zhong, Lina M Olsson, Vilma Urbonaviciute, Min Yang, Liselotte Bäckdahl, Rikard Holmdahl
A single nucleotide polymorphism in Ncf1 has been found with a major effect on chronic inflammatory autoimmune diseases in the rat with the surprising observation that a lower reactive oxygen response led to more severe diseases. This finding was subsequently reproduced in the mouse and the effect operates in many different murine diseases through different pathogenic pathways; like models for rheumatoid arthritis, encephalomyelitis, lupus, gout, psoriasis and psoriatic arthritis. The human gene is located in an unstable region with many variable sequence repetitions, which means it has not been included in any genome wide associated screens so far...
March 8, 2018: Free Radical Biology & Medicine
Marta Consuegra-Fernández, Feng Lin, David A Fox, Francisco Lozano
CD6 is a cell surface glycoprotein expressed by most T cells and a subset of B cells that has incompletely-defined roles in regulation of lymphocyte development, selection, activation and differentiation. The two main known mammalian CD6 ligands, CD166/ALCAM and the very recently reported CD318, are widely expressed by both immune cells and a wide range of other cell types, including various epithelial and mesenchymal cell types, as well as many neoplasms. Moreover, CD6 is also a receptor for several pathogen- and damage-associated molecular patterns...
March 8, 2018: Autoimmunity Reviews
Mark Barbour, Rachel Wood, Shehla U Hridi, Chelsey Wilson, Grant McKay, Trevor J Bushell, Hui-Rong Jiang
Experimental autoimmune encephalomyelitis (EAE) mice were administered with murine anti-CD52 antibody to investigate its therapeutic effect and whether the treatment modulates IL-33 and ST2 expression. EAE severity and central nervous system (CNS) inflammation were reduced following the treatment, which was accompanied by peripheral T and B lymphocyte depletion and reduced production of various cytokines including IL-33, while sST2 was increased. In spinal cords of EAE mice, while the number of IL-33+ cells remained unchanged, the extracellular level of IL-33 protein was significantly reduced in anti-CD52 antibody treated mice compared with controls...
February 24, 2018: Journal of Neuroimmunology
L Monge Galindo, A L Martínez de Morentín, V Pueyo Royo, J P García Iñiguez, S Sánchez Marco, J López-Pisón, J L Peña-Segura
INTRODUCTION AND OBJECTIVE: In this article, we present our experience on optic neuritis (ON) and provide a diagnostic/therapeutic protocol, intended to rule out other aetiologies (particularly infection), and a fact sheet for parents. MATERIAL AND METHODS: We conducted a descriptive, retrospective study of patients with ON over a 27-year period (1990-2017). A review of the available scientific evidence was performed in order to draft the protocol and fact sheet...
March 8, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Fiona Newberry, Shen-Yuan Hsieh, Tom Wileman, Simon R Carding
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome...
March 15, 2018: Clinical Science (1979-)
Valentin Mutemberezi, Baptiste Buisseret, Julien Masquelier, Owein Guillemot-Legris, Mireille Alhouayek, Giulio G Muccioli
BACKGROUND: Oxysterols are cholesterol derivatives that have been suggested to play a role in inflammatory diseases such as obesity, atherosclerosis, or neuroinflammatory diseases. However, the effect of neuroinflammation on oxysterol levels has only been partially studied so far. METHODS: We used an HPLC-MS method to quantify over ten oxysterols both in in vitro and in vivo models of neuroinflammation. In the same models, we used RT-qPCR to analyze the expression of the enzymes responsible for oxysterol metabolism...
March 9, 2018: Journal of Neuroinflammation
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