B cell function impacts the efficacy of IFN- β therapy in EAE

Recent studies identified that interferon beta (IFN- β) treatment skews B-cells towards a regulatory phenotype in multiple sclerosis. To assess B cell involvement during IFN-β therapy, we compared IFN-β treatment in a B cell-independent model and a B cell-dependent model of experimental autoimmune encephalomyelitis (EAE). We show that in B cell-ind ependent EAE, IFN-β ameliorates neuroinflammation. Conversely, in B cell-dependent EAE IFN-β has no effect on disease. Effective IFN-β therapy in B cell-independent EAE was associated with reduced inflammatory T cells in the CNS and skewed splenic B cells towards an immature population and away f rom a germinal center population.
Source: Journal of Neuroimmunology - Category: Allergy & Immunology Authors: Source Type: research

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CONCLUSIONOur findings suggest that CSF levels of the NLRP3 inflammasome may serve as a diagnostic biomarker for distinguishing NMOSD and MS. Pyroptosis mediated by the NLRP3 inflammasome following mitochondrial damage may play an important role in the pathogenesis of these neuroinflammatory disorders, especially NMOSD.Graphical abstract
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Publication date: Available online 5 December 2019Source: CellAuthor(s): Chun-Cheih Chao, Cristina Gutiérrez-Vázquez, Veit Rothhammer, Lior Mayo, Michael A. Wheeler, Emily C. Tjon, Stephanie E.J. Zandee, Manon Blain, Kalil Alves de Lima, Maisa C. Takenaka, Julian Avila-Pacheco, Patrick Hewson, Lei Liu, Liliana M. Sanmarco, Davis M. Borucki, Gabriel Z. Lipof, Sunia A. Trauger, Clary B. Clish, Jack P. Antel, Alexandre PratSummaryMetabolism has been shown to control peripheral immunity, but little is known about its role in central nervous system (CNS) inflammation. Through a combination of proteomic, metabolomi...
Source: Cell - Category: Cytology Source Type: research
The U.S. Food and Drug Administration has approved three applications for first generics of Gilenya (fingolimod) capsules for the treatment of relapsing forms of multiple sclerosis (MS) in adult patients. MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body.
Source: World Pharma News - Category: Pharmaceuticals Tags: Featured FDA Regulatory Affairs Source Type: news
Conclusion: The downregulation in the expression of QKI-V5 in the blood of patients with CNS-inflammatory-demyelinating-diseases and in the brain and blood of EAE mice is likely caused by a circulating factor and might promote re-myelination by regulation of myelin-associated genes. Key words: QKI variants, Multiple sclerosis (MS), Neuromyelitis optica (NMO), Astrocytes, Demyelination
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
In conclusion, T2D impairs vascular function by dysregulated autophagy. Therefore, autophagy could be a potential target for overcoming diabetic microvascular complications. To What Degree Does Loss of Skeletal Muscle with Age Contribute to Immunosenescence? https://www.fightaging.org/archives/2019/11/to-what-degree-does-loss-of-skeletal-muscle-with-age-contribute-to-immunosenescence/ Sarcopenia, the progressive loss of muscle mass and strength, is characteristic of aging. A perhaps surprisingly large fraction of the losses can be averted by strength training, but there are nonetheless inexorable process...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: De Silvestri A, Capittini C, Mallucci G, Bergamaschi R, Rebuffi C, Pasi A, Martinetti M, Tinelli C Abstract Multiple Sclerosis (MS) displays a heterogeneous clinical onset and progression, which are mostly unpredictable, but demyelination of the central nervous system (CNS) leads to substantial deficits of sensory, motor, autonomic, and neurocognitive functions. Considering all genetic studies on MS, including the advanced genome-wide association studies, the risk linked to HLA alleles remains the highest among other susceptibility genetic variants. However, given the genetic variability of HLA alleles in ...
Source: Disease Markers - Category: Laboratory Medicine Tags: Dis Markers Source Type: research
In this study, we investigated the role of TNFR2 expressed in the oligodendrocyte in the early phase of EAE pathogenesis. We demonstrated that mice with specific ablation of oligodendroglial TNFR2 displayed early onset and higher peak of motor dysfunction when subjected to EAE, in advance of which accelerated infiltration of immune cells was observed as early as 10 days post EAE induction. The immune cell influx was preceded by microglial activation and increased blood brain barrier permeability. Lack of oligodendroglial TNFR2 accelerated the expression of inflammatory cytokines as well as expression and activation of the ...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
Researchers here note a signature of blood-brain barrier dysfunction that is common in many forms of damage and injury to the brain, suggesting it to be more broadly relevant to pathology than suspected. There is already good evidence for dysfunction of the blood-brain barrier to be an early feature of neurodegenerative diseases. The specialized cells of the blood-brain barrier line blood vessels that pass through the central nervous system, managing the passage of molecules and cells. When the barrier fails, unwanted molecules such as fibrogen can enter the brain to cause inflammation - and chronic inflammation in the bra...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Publication date: Available online 25 November 2019Source: Multiple Sclerosis and Related DisordersAuthor(s): Amy Kunchok, Charles Malpas, Petra Nytrova, Eva Kubala Havrdova, Raed Alroughani, Murat Terzi, Bassem Yamout, Jyh Yung Hor, Rana Karabudak, Cavit Boz, Serkan Ozakbas, Javier Olascoaga, Magdolna Simo, Franco Granella, Francesco Patti, Pamela McCombe, Tunde Csepany, Bhim Singhal, Roberto Bergamaschi, Yara FragosoABSTRACTBackgroundAquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typicall...
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Women have increased prevalence of Th17-mediated autoimmune diseases, including lupus and multiple sclerosis, and severe asthma. While estradiol and progesterone increased IL-17A production in Th17 cells by inhibiting Let7f miRNA expression and increasing IL-23 receptor (IL-23R) expression, it remained unclear how estrogen signaling through the canonical nuclear receptors, estrogen receptor α (ERα) and/or ERβ, regulated this pathway. We hypothesized that estrogen signaling through ERα increased IL-23R expression and IL-17A production from Th17 cells. To test this hypothesis, naïve T cells from W...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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