Vitamin D3-mediated resistance to a multiple sclerosis model disease depends on myeloid cell 1,25-dihydroxyvitamin D3 synthesis and correlates with increased CD4+ T cell CTLA-4 expression

Microglial cell activation is the earliest biomarker of the inflammatory processes that cause central nervous system (CNS) lesions in multiple sclerosis. We hypothesized that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) production by activated microglia and macrophages in the CNS inhibits these inflammatory processes. To test this hypothesis, we targeted the Cyp27b1 gene specifically in myeloid cells, then analyzed the influence of disrupted myeloid cell 1,25-(OH)2D3 synthesis on vitamin D3-mediated resistance to experimental autoimmune encephalomyelitis (EAE).
Source: Journal of Neuroimmunology - Category: Allergy & Immunology Authors: Source Type: research

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ConclusionThe 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
CONCLUSION: Our study showed decreased antioxidant capacity in newly diagnosed MS patients compared to controls. We failed to find association of subclinical atherosclerosis with oxidative stress in newly diagnosed MS. PMID: 31816220 [PubMed - as supplied by publisher]
Source: Neuroendocrinology Letters - Category: Endocrinology Tags: Neuro Endocrinol Lett Source Type: research
AbstractThe renin angiotensin system (RAS), which is classically known for blood pressure regulation, has functions beyond this. There are two axes of RAS that work to counterbalance each other and are active throughout the body, including the CNS. The pathological axis, consisting of angiotensin II (A1-8), angiotensin converting enzyme (ACE) and the angiotensin II type 1 receptor (AT1R), is upregulated in many CNS diseases, including multiple sclerosis (MS). MS is an autoimmune and neurodegenerative disease of the CNS characterized by inflammation, demyelination and axonal degeneration. Published research has described in...
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research
UCLA scientists have discovered one reason why autoimmune diseases are more prevalent in women than in men. While males inherit their mother ’s X chromosome and father’s Y chromosome, females inherit X chromosomes from both parents. New research, which shows differences in how each of those X chromosomes is regulated, suggests that the X chromosome that females get from their father may help to explain their more active immune system .“It’s been known for many years that women are more susceptible to autoimmune diseases than men are,” said lead study author Dr. Rhonda Voskuhl, a UCLA professor...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
In conclusion, our data suggest that DKI and microstructural modeling can provide a unique contrast capable of detecting EAE-specific changes correlating with clinical disability.
Source: NeuroImage - Category: Neuroscience Source Type: research
Contributors : David Schafflick ; Maike Hartlenert ; Andreas Schulte-Mecklenbeck ; Tobias Lautwein ; Jolien Wolbert ; Gerd M HorsteSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensCerebrospinal fluid (CSF) protects the central nervous system (CNS) and analyzing CSF aids the diagnosis of CNS diseases, but our understanding of CSF leukocytes remains superficial. Here, using single cell transcriptomics, we identified a specific border-associated composition and transcriptome of CSF leukocytes. Multiple sclerosis (MS) – an autoimmune disease of the CNS – increased transcription...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
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
Abstract Experimental autoimmune encephalomyelitis (EAE) is a commonly used mouse model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination leading to brain and spinal cord malfunctions. We postulate that not only biological but also biomechanical properties play an important role in CNS function impairments. Atomic force microscopy (AFM) was applied to investigate mechanical properties of spinal cords collected from EAE mice in preonset, onset, peak, and chronic disease phases. Biomechanical changes were compared with histopathological alteratio...
Source: Archives of Biochemistry and Biophysics - Category: Biochemistry Authors: Tags: Arch Biochem Biophys 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
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