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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
#1
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
#2
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, Yungjiao 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...
September 11, 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
#3
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
#4
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
#5
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
#6
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
#7
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...
July 28, 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
#8
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
#9
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...
July 8, 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
#10
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
#11
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
#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/28642148/biological-activity-of-glatiramer-acetate-on-treg-and-anti-inflammatory-monocytes-persists-for-more-than-10years-in-responder-multiple-sclerosis-patients
#13
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
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/28599652/regulatory-t-cells-in-multiple-sclerosis-and-myasthenia-gravis
#15
REVIEW
K M Danikowski, S Jayaraman, B S Prabhakar
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs)...
June 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28599286/decitabine-inhibits-t-cell-proliferation-via-a-novel-tet2-dependent-mechanism-and-exerts-potent-protective-effect-in-mouse-auto-and-allo-immunity-models
#16
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)...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536579/peripherally-induced-regulatory-t-cells-recruited-protectors-of-the-central-nervous-system-against-autoimmune-neuroinflammation
#17
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/28533380/ccr8-foxp3-treg-cells-as-master-drivers-of-immune-regulation
#18
Yiftah Barsheshet, Gizi Wildbaum, Eran Levy, Alon Vitenshtein, Chika Akinseye, Jeremy Griggs, Sergio A Lira, Nathan Karin
The current study identifies CCR8(+) regulatory T cells (Treg cells) as drivers of immunosuppression. We show that in human peripheral blood cells, more than 30% of Treg up-regulate CCR8 following activation in the presence of CCL1. This interaction induces STAT3-dependent up-regulation of FOXp3, CD39, IL-10, and granzyme B, resulting in enhanced suppressive activity of these cells. Of the four human CCR8 ligands, CCL1 is unique in potentiating Treg cells. The relevance of these observations has been extended using an experimental model of multiple sclerosis [experimental autoimmune encephalomyelitis, (EAE)] and a stabilized version of mouse CCL1 (CCL1-Ig)...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28498568/reconstitution-of-immune-cell-populations-in-multiple-sclerosis-patients-after-autologous-stem-cell-transplantation
#19
REVIEW
F G Karnell, D Lin, S Motley, T Duhen, N Lim, D J Campbell, L A Turka, H T Maecker, K M Harris
Multiple sclerosis is an inflammatory T cell-mediated autoimmune disease. In a Phase II clinical trial, high-dose immunosuppressive therapy combined with autologous CD34(+) haematopoietic stem cell transplant resulted in 69·2% of subjects remaining disease-free without evidence of relapse, loss of neurological function or new magnetic resonance imaging (MRI) lesions to year 5 post-treatment. A combination of CyTOF mass cytometry and multi-parameter flow cytometry was used to explore the reconstitution kinetics of immune cell subsets in the periphery post-haematopoietic cell transplant (HSCT) and the impact of treatment on the phenotype of circulating T cells in this study population...
September 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28493107/beyond-immunomodulation-the-regenerative-role-for-regulatory-t-cells-in-central-nervous-system-remyelination
#20
REVIEW
Veronique E Miron
Central nervous system regeneration after injury can occur in the form of remyelination, the reinstatement of myelin around axons which restores axon health and function. However, remyelination often fails in chronic neurological diseases, such as progressive multiple sclerosis. The lack of currently approved pro-remyelination therapies highlights the need to elucidate the cellular and molecular mechanisms underpinning this regenerative process. Whereas some T lymphocyte subsets such as Th1 and Th17 are implicated in inducing myelin injury, a recent study by Dombrowski et al...
June 2017: Journal of Cell Communication and Signaling
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