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https://www.readbyqxmd.com/read/29118761/immunological-and-clinical-effect-of-diet-modulation-of-the-gut-microbiome-in-multiple-sclerosis-patients-a-pilot-study
#1
Marina Saresella, Laura Mendozzi, Valentina Rossi, Franca Mazzali, Federica Piancone, Francesca LaRosa, Ivana Marventano, Domenico Caputo, Giovanna E Felis, Mario Clerici
Pathogenesis of autoimmune disorders, including multiple sclerosis (MS), has been linked to an alteration of the resident microbial commensal community and of the interplay between the microbiota and the immune system. Dietary components such as fiber, acting on microbiota composition, could, in principle, result in immune modulation and, thus, could be used to obtain beneficial outcomes for patients. We verified this hypothesis in a pilot study involving two groups of clinically similar relapsing-remitting (RR) MS patients who had undergone either a high-vegetable/low-protein diet (HV/LP diet group; N = 10) or a "Western Diet" (WD group; N = 10) for at least 12 months...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29051763/il-12p35-inhibits-neuroinflammation-and-ameliorates-autoimmune-encephalomyelitis
#2
Jin Kyeong Choi, Ivy M Dambuza, Chang He, Cheng-Rong Yu, Anita N Uche, Mary J Mattapallil, Rachel R Caspi, Charles E Egwuagu
Multiple sclerosis (MS) is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL-35 cytokine, might be an effective biologic for suppressing neuroinflammatory responses and ameliorating the pathology of experimental autoimmune encephalomyelitis (EAE), the mouse model of human MS. We further show that IL-12p35 conferred protection from neuropathy by inhibiting the expansion of pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells into the brain and spinal cord...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29018225/s1p1-deletion-differentially-affects-th17-and-regulatory-t-cells
#3
Ahmet Eken, Rebekka Duhen, Akhilesh K Singh, Mallory Fry, Jane H Buckner, Mariko Kita, Estelle Bettelli, Mohamed Oukka
Sphingosine-1 phosphate receptor 1 (S1P1) is critical for the egress of T and B cells out of lymphoid organs. Although S1P1 agonist fingolimod is currently used for the treatment of multiple sclerosis (MS) little is known how S1P1 signaling regulates Th17 and Treg cell homeostasis. To study the impact of S1P1 signaling on Th17 and Treg cell biology, we specifically deleted S1P1 in Th17 and Treg cells using IL-17A (Cre) and Foxp3 (Cre) mice, respectively. Deletion of S1P1 in Th17 cells conferred resistance to experimental autoimmune encephalomyelitis (EAE)...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28983300/human-tregs-made-antigen-specific-by-gene-modification-the-power-to-treat-autoimmunity-and-antidrug-antibodies-with-precision
#4
REVIEW
Patrick R Adair, Yong Chan Kim, Ai-Hong Zhang, Jeongheon Yoon, David W Scott
Human regulatory CD4(+) T cells (Tregs) are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. This research has opened the doors for Tregs as a potential therapeutic for diseases and disorders such as multiple sclerosis, type I diabetes, transplantation, and immune responses to protein therapeutics, like factor VIII...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28962999/nr4a1-plays-a-crucial-modulatory-role-in-th1-th17-cell-responses-and-cns-autoimmunity
#5
Li-Mei Wang, Yuan Zhang, Xing Li, Ming-Liang Zhang, Lin Zhu, Guang-Xian Zhang, Yu-Ming Xu
Nuclear receptor4 group A1 (Nr4a1), an orphan nuclear receptor, is down-regulated in peripheral blood mononuclear cells (MNCs) of individuals with multiple sclerosis (MS), and Nr4a1 deficiency results in severe experimental autoimmune encephalomyelitis (EAE), an animal model of MS, caused by increased macrophage infiltration into the central nervous system (CNS). However, the role of Nr4a1 in macrophage phenotype and T cell responses remains poorly understood. In the present study we show that macrophages/microglia of Nr4a1(-/-) mice, which exhibited earlier onset and more severe clinical EAE, were polarized to an enhanced type 1 (M1) phenotype and produced higher levels of IL-12 and TNF-α than wild type mice...
September 26, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28946394/bifidobacterium-animalis-in-combination-with-human-origin-of-lactobacillus-plantarum-ameliorate-neuroinflammation-in-experimental-model-of-multiple-sclerosis-by-altering-cd4-t-cell-subset-balance
#6
Zohre Salehipour, Dariush Haghmorad, Mojtaba Sankian, Maryam Rastin, Reza Nosratabadi, Mohammad Mehdi Soltan Dallal, Nafiseh Tabasi, Mahdieh Khazaee, Leila Roozbeh Nasiraii, Mahmoud Mahmoudi
BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Recent reports have shown that probiotics can induce immunomodulatory activity with promising effects in inflammatory diseases. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of Lactobacillus plantarum A7, which comprises human commensal bacteria, and Bifidobacterium animalis, a potential probiotic strain, on alleviation of experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28943274/gene-therapy-induced-antigen-specific-tregs-inhibit-neuro-inflammation-and-reverse-disease-in-a-mouse-model-of-multiple-sclerosis
#7
Geoffrey D Keeler, Sandeep Kumar, Brett Palaschak, Emily L Silverberg, David M Markusic, Noah T Jones, Brad E Hoffman
The devastating neurodegenerative disease multiple sclerosis (MS) could substantially benefit from an adeno-associated virus (AAV) immunotherapy designed to restore a robust and durable antigen-specific tolerance. However, developing a sufficiently potent and lasting immune-regulatory therapy that can intervene in ongoing disease is a major challenge and has thus been elusive. We addressed this problem by developing a highly effective and robust tolerance-inducing in vivo gene therapy. Using a pre-clinical animal model, we designed a liver-targeting gene transfer vector that expresses full-length myelin oligodendrocyte glycoprotein (MOG) in hepatocytes...
September 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28915632/decitabine-inhibits-t-cell-proliferation-via-a-novel-tet2-dependent-mechanism-and-exerts-potent-protective-effect-in-mouse-auto-and-allo-immunity-models
#8
Xue Wang, Jun Wang, Yong Yu, Tonghui Ma, Ping Chen, Bing Zhou, Ran Tao
Multiple sclerosis (MS) is an autoimmune disease characterized by the dysregulated immune response including innate and adaptive immune responses. Increasing evidence has proven the importance of epigenetic modification in the progression of MS. Recent studies revealed that low-dose decitabine (Dec, 5-Aza-2'-deoxycytidine), which incorporates into replicating DNA and inhibits DNA methylation, could prevent experimental autoimmune encephalomyelitis (EAE) development by increasing the number of regulatory T cells (Tregs)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893978/gut-bacteria-from-multiple-sclerosis-patients-modulate-human-t-cells-and-exacerbate-symptoms-in-mouse-models
#9
Egle Cekanaviciute, Bryan B Yoo, Tessel F Runia, Justine W Debelius, Sneha Singh, Charlotte A Nelson, Rachel Kanner, Yadira Bencosme, Yun Kyung Lee, Stephen L Hauser, Elizabeth Crabtree-Hartman, Ilana Katz Sand, Mar Gacias, Yunjiao Zhu, Patrizia Casaccia, Bruce A C Cree, Rob Knight, Sarkis K Mazmanian, Sergio E Baranzini
The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28843039/tnf-tnf-inducers-and-tnfr2-agonists-a-new-path-to-type-1-diabetes-treatment
#10
REVIEW
Denise L Faustman
BACKGROUND: In the past decade, interest in the century-old tuberculosis vaccine, bacillus Calmette-Guerin (BCG), has been revived for potential new therapeutic uses in type 1 diabetes and other forms of autoimmunity. METHODS: Diverse clinical trials are now proving the value of BCG in prevention and treatment of type 1 diabetes, in the treatment of new onset multiple sclerosis and other immune conditions. BCG contains the avirulent tuberculosis strain Mycobacterium bovis, a vaccine originally developed for tuberculosis prevention...
August 26, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28793364/melatonin-reduces-inflammatory-response-in-peripheral-t-helper-lymphocytes-from-relapsing-remitting-multiple-sclerosis-patients
#11
Nuria Álvarez-Sánchez, Ivan Cruz-Chamorro, María Díaz-Sánchez, Helia Sarmiento-Soto, Pablo Medrano-Campillo, Alicia Martínez-López, Patricia J Lardone, Juan M Guerrero, Antonio Carrillo-Vico
Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system in which the immune system plays a central role. In particular, effector populations such as T helper (Th) 1, Th9, Th17, and Th22 cells are involved in disease development, whereas T regulatory cells (Tregs) are associated with the resolution of the disease. Melatonin levels are impaired in patients with MS, and exogenous melatonin ameliorates the disease in MS animal models by modulating the Th1/Th17/Treg responses and also improves quality of life and several symptoms in patients with MS...
August 9, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28782487/natalizumab-changes-the-peripheral-profile-of-the-th17-panel-in-ms-patients-new-mechanisms-of-action
#12
Rodica Ioana Bălașa, Simu Mihaela, Septimiu Voidăzan, Laura Iulia Bărcuțean, Zoltan Bajko, Adina Huțanu, Iunius Simu, Smaranda Maier
INTRODUCTION: Natalizumab (NAT) is an effective treatment for relapsing remitting multiple sclerosis (RRMS),as it makes the blood-brain-barrier impenetrable bybinding to the α4integrin subunit. The objectives of our study were to find new peripheral mechanisms of action of NAT and new biomarkers of treatment response. MATERIAL AND METHODS: We prospectively assessed the serum levels of 15 cytokines from the Th17 Cytokine Panelusing Bio-plex Pro Human in a group of 29 RRMS patients treated with NAT and 29 healthy subjects(HS) at inclusion and after 8 months of NAT treatment...
August 7, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28769921/microrna-181-variants-regulate-t-cell-phenotype-in-the-context-of-autoimmune-neuroinflammation
#13
Samira Ghorbani, Farideh Talebi, Wing Fuk Chan, Farimah Masoumi, Mohammed Vojgani, Christopher Power, Farshid Noorbakhsh
BACKGROUND: Recent studies have revealed that multiple sclerosis (MS) lesions have distinct microRNA (miRNA) expression profiles. miR-181 family members show altered expression in MS tissues although their participation in MS pathogenesis remains uncertain. Herein, we investigated the involvement of miR-181a and miR-181b in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). METHODS: miR-181a and -b levels were measured in the central nervous system (CNS) of patients with MS and mice with EAE as well as relevant leukocyte cultures by real-time RT-PCR...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28755038/experimental-autoimmune-encephalomyelitis-ameliorated-by-passive-transfer-of-polymerase-1-silenced-mog35-55-lymphatic-node-cells-verification-of-a-novel-therapeutic-approach-in-multiple-sclerosis
#14
R Zilkha-Falb, M Gurevich, A Achiron
In the current study, we present an innovative concept based on the knowledge that enhancing naturally occurring biological mechanisms is effective in preventing neuronal damage and maintaining low disease activity in about 15% of multiple sclerosis (MS) patients presenting the benign type of MS. Recently, we have demonstrated that low disease activity in benign MS is associated with suppression of RNA polymerase 1 (POL1) pathway; therefore, targeting POL1 transcription machinery as a strategy for suppressing active forms of MS is suggested...
September 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28690849/altered-regulatory-t-cell-fractions-and-helios-expression-in-clinically-isolated-syndrome-clues-to-the-development-of-multiple-sclerosis
#15
Anderson P Jones, Stephanie Trend, Scott N Byrne, Marzena J Fabis-Pedrini, Sian Geldenhuys, David Nolan, David R Booth, William M Carroll, Robyn M Lucas, Allan G Kermode, Prue H Hart
Development of multiple sclerosis (MS) is frequently preceded by an acute or subacute neurological disturbance referred to as clinically isolated syndrome (CIS). The specific immunological disturbances present in CIS remain underexamined. This study analysed peripheral blood mononuclear cells from n=18 treatment-naive individuals with recently diagnosed CIS (<120 days) for disturbances in the phenotype of T regulatory (Treg), follicular T regulatory (Tfr), T helper (Th), follicular T helper (Tfh) and B cells...
May 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28689297/estrogen-protects-both-sexes-against-eae-by-promoting-common-regulatory-cell-subtypes-independent-of-endogenous-estrogen
#16
Hilary A Seifert, Gil Benedek, Ha Nguyen, Gail Kent, Arthur A Vandenbark, Halina Offner
Autoimmune diseases including multiple sclerosis predominantly affect females. Although high levels of sex hormones, particularly estrogen (E2), can reduce proinflammatory immune responses, it remains unclear if a lack of endogenous sex hormones might affect treatment with exogenous sex hormones. Pretreatment with E2 almost completely prevents intact female and male mice from developing clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) by promoting various regulatory immune cell phenotypes...
October 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28686480/caerulomycin-a-suppresses-the-differentiation-of-na%C3%A3-ve-t-cells-and-alleviates-the-symptoms-of-experimental-autoimmune-encephalomyelitis
#17
Weshely Kujur, Rama Krishna Gurram, Sudeep K Maurya, Sajid Nadeem, Sathi Babu Chodisetti, Nargis Khan, Javed Naim Agrewala
Multiple sclerosis (MS) is a highly detrimental autoimmune disease of the central nervous system. There is no cure for it but the treatment typically focuses on subsiding severity and recurrence of the disease. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. It is characterized by frequent relapses due to the generation of memory T cells. Caerulomycin A (CaeA) is known to suppress the Th1 cells, Th2 cells, and Th17 cells. Interestingly, it enhances the generation of regulatory T cells (Tregs)...
July 7, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28650992/galectin-8-as-an-immunosuppressor-in-experimental-autoimmune-encephalomyelitis-and-a-target-of-human-early-prognostic-antibodies-in-multiple-sclerosis
#18
Evelyn Pardo, Claudia Cárcamo, Reinaldo Uribe-San Martín, Ethel Ciampi, Fabián Segovia-Miranda, Cristobal Curkovic-Peña, Fabián Montecino, Christopher Holmes, Juan Enrique Tichauer, Eric Acuña, Francisco Osorio-Barrios, Marjorie Castro, Priscilla Cortes, Claudia Oyanadel, David M Valenzuela, Rodrigo Pacheco, Rodrigo Naves, Andrea Soza, Alfonso González
Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients...
2017: PloS One
https://www.readbyqxmd.com/read/28646573/interferon-%C3%AE-regulates-dendritic-cell-activation-and-migration-in-experimental-autoimmune-encephalomyelitis
#19
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-β (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 neurological impairment compared with IFN-β(+/+) mice...
November 2017: Immunology
https://www.readbyqxmd.com/read/28642148/biological-activity-of-glatiramer-acetate-on-treg-and-anti-inflammatory-monocytes-persists-for-more-than-10years-in-responder-multiple-sclerosis-patients
#20
Michela Spadaro, Francesca Montarolo, Simona Perga, Serena Martire, Federica Brescia, Simona Malucchi, Antonio Bertolotto
Glatiramer acetate (GA) is a widely used treatment for multiple sclerosis (MS), with incompletely defined mechanism of action. Short-term studies suggested its involvement in the modulation of anti-inflammatory cytokines and regulatory T cells (Treg), while long-term effect is still unknown. To investigate this aspect, we analyzed by flow-cytometry peripheral-blood Treg, natural killer (NK), CD4 and CD8 T-cells and anti-inflammatory CD14(+)CD163(+) monocytes from 37 healthy donor and 90 RRMS patients divided in untreated, treated with GA for 12months and from 34 to 192months...
August 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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