14,872 results match your criteria autoimmune encephalomyelitis

Murine endometrial-derived mesenchymal stem cells suppress experimental autoimmune encephalomyelitis depending on indoleamine-2,3-dioxygenase expression.

Clin Sci (Lond) 2021 May;135(9):1065-1082

Neuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo (USP), São Paulo, SP, Brazil.

Cellular therapy with mesenchymal stem cells (MSCs) is a huge challenge for scientists, as little translational relevance has been achieved. However, many studies using MSCs have proved their suppressive and regenerative capacity. Thus, there is still a need for a better understanding of MSCs biology and the establishment of newer protocols, or to test unexplored tissue sources. Read More

View Article and Full-Text PDF

Dendritic cell PIK3C3/VPS34 controls the pathogenicity of CNS autoimmunity independently of LC3-associated phagocytosis.

Autophagy 2021 May 7:1-10. Epub 2021 May 7.

Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.

PIK3C3/VPS34 is a key player in macroautophagy/autophagy and MAP1LC3/LC3-associated phagocytosis (LAP), which play critical roles in dendritic cell (DC) function. In this study, we assessed the contribution of PIK3C3 to DC function during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We found that -deficient DCs exhibit attenuated capacity to reactivate encephalitogenic T cells in the central nervous system, leading to reduced incidence and severity of EAE in DC-specific -deficient mice. Read More

View Article and Full-Text PDF

Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy.

Cell Mol Immunol 2021 May 6. Epub 2021 May 6.

Division of Immunology, LCMN, Germans Trias i Pujol University Hospital and Research Institute, Barcelona, Spain.

Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Read More

View Article and Full-Text PDF

Molecular effects of curcumin on the experimental autoimmune encephalomyelitis.

Vet Res Forum 2021 15;12(1):47-52. Epub 2021 Mar 15.

Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). Previous studies have shown that myelin degradation during MS and EAE resulted in reduced expression of some of the proteins, e.g. Read More

View Article and Full-Text PDF

Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms.

Nat Commun 2021 05 5;12(1):2547. Epub 2021 May 5.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.

Receptors and their ligands are important therapeutic targets for about one third of marketed drugs. Here, we describe an epitope-guided approach for selection of antibodies that modulate cellular signaling of targeted receptors. We chose CXC chemokine receptor 2 (CXCR2) in the G-protein coupled receptor superfamily as receptor and a CXCR2 N-terminal peptide for antibody selection. Read More

View Article and Full-Text PDF

Learning-Dependent Dendritic Spine Plasticity Is Impaired in Spontaneous Autoimmune Encephalomyelitis.

Dev Neurobiol 2021 May 4. Epub 2021 May 4.

Department of Anesthesiology, New York University School of Medicine, New York, NY, USA.

Cognitive impairment is often observed in multiple sclerosis and its animal models, experimental autoimmune encephalomyelitis (EAE). Using mice with immunization-induced EAE, we have previously shown that the stability of cortical synapses is markedly decreased before the clinical onset of EAE. In this study, we examined learning-dependent structural synaptic plasticity in a spontaneous EAE model. Read More

View Article and Full-Text PDF

Matrine treatment reduces retinal ganglion cell apoptosis in experimental optic neuritis.

Sci Rep 2021 May 4;11(1):9520. Epub 2021 May 4.

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Read More

View Article and Full-Text PDF

Identification of a Long Noncoding RNA as Key Regulator of IL-17 Signaling through the SRSF10-IRF1-Act1 Axis in Autoimmune Diseases.

J Immunol 2021 May 3. Epub 2021 May 3.

Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China

IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA, , regulates Act1 expression and IL-17A signaling by recruiting SRSF10, which downregulates the expression of IRF1, a transcriptional factor of Act1. Read More

View Article and Full-Text PDF

Lipid Receptor G2A-Mediated Signal Pathway Plays a Critical Role in Inflammatory Response by Promoting Classical Macrophage Activation.

J Immunol 2021 May 3. Epub 2021 May 3.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

Macrophage polarization is a dynamic and integral process in tissue inflammation and remodeling. In this study, we describe that lipoprotein-associated phospholipase A (Lp-PLA) plays an important role in controlling inflammatory macrophage (M1) polarization in rodent experimental autoimmune encephalomyelitis (EAE) and in monocytes from multiple sclerosis (MS) patients. Specific inhibition of Lp-PLA led to an ameliorated EAE via markedly decreased inflammatory and demyelinating property of M1. Read More

View Article and Full-Text PDF

Ponesimod modulates the Th1/Th17/Treg cell balance and ameliorates disease in experimental autoimmune encephalomyelitis.

J Neuroimmunol 2021 Apr 23;356:577583. Epub 2021 Apr 23.

Department of Neurology, Key Laboratory of Hebei Neurology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China. Electronic address:

Sphingosine-1-phosphate receptor 1 (S1P1) plays an important role in autoimmune disease. Here, we evaluated whether ponesimod, an S1P1 modulator, affects inflammation in experimental autoimmune encephalomyelitis (EAE) and investigated Th1/Th2/Th17/Treg cell subsets. Ponesimod treatment ameliorated EAE and alleviated inflammatory infiltration. Read More

View Article and Full-Text PDF

Identification of TAPBPL as a novel negative regulator of T-cell function.

EMBO Mol Med 2021 May 3;13(5):e13404. Epub 2021 May 3.

Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.

T cell stimulatory and inhibitory molecules are critical for the regulation of immune responses. In this study, we identify a novel T cell co-inhibitory molecule TAPBPL, whose amino acid sequence shares homology with known B7 family members. TAPBPL protein is expressed on resting and activated T cells, B cells, monocytes, and dendritic cells (DCs), as well as on some tumor tissues. Read More

View Article and Full-Text PDF

Central Nervous System Barriers Impact Distribution and Expression of iNOS and Arginase-1 in Infiltrating Macrophages During Neuroinflammation.

Front Immunol 2021 15;12:666961. Epub 2021 Apr 15.

Theodor Kocher Institute, University Bern, Bern, Switzerland.

In multiple sclerosis (MS) and other neuroinflammatory diseases, monocyte-derived cells (MoCs) traffic through distinct central nervous system (CNS) barriers and gain access to the organ parenchyma exerting detrimental or beneficial functions. How and where these MoCs acquire their different functional commitments during CNS invasion remains however unclear, thus hindering the design of MS treatments specifically blocking detrimental MoC actions. To clarify this issue, we investigated the distribution of iNOS pro-inflammatory and arginase-1 anti-inflammatory MoCs at the distinct border regions of the CNS in a mouse model of MS. Read More

View Article and Full-Text PDF

LRRC4 functions as a neuron-protective role in experimental autoimmune encephalomyelitis.

Mol Med 2021 05 1;27(1):44. Epub 2021 May 1.

Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, 410013, Hunan, China.

Background: Leucine rich repeat containing 4 (LRRC4), also known as netrin-G ligand-2 (NGL-2), belongs to the superfamily of LRR proteins and serves as a receptor for netrin-G2. LRRC4 regulates the formation of excitatory synapses and promotes axon differentiation. Mutations in LRRC4 occur in Autism Spectrum Disorder (ASD) and intellectual disability. Read More

View Article and Full-Text PDF

Docosahexaenoic acid ameliorates autoimmune inflammation by activating GPR120 signaling pathway in dendritic cells.

Int Immunopharmacol 2021 Apr 28;97:107698. Epub 2021 Apr 28.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China; Department of Pathology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States. Electronic address:

Although the phenomenon that omega-3 polyunsaturated fatty acids (n-3 PUFAs) shows to have a beneficial effect in patients suffering from multiple sclerosis (MS) and other autoimmune diseases has been empirically well-documented, the molecular mechanisms that underline the anti-inflammatory effects of n-3 PUFAs are yet to be understood. In experimental autoimmune encephalomyelitis (EAE), a model for MS, we show that one of the underlying mechanisms by which dietary docosahexaenoic acid (DHA) exerts its anti-inflammatory effect is regulating the functional activities of dendritic cells (DCs). In DHA-treated EAE mice, DCs acquire a regulatory phenotype characterized by low expression of co-stimulatory molecules, decreased production of pro-inflammatory cytokines, and enhanced capability of regulatory T-cell induction. Read More

View Article and Full-Text PDF

miR-451a levels rather than human papillomavirus vaccine administration is associated with the severity of murine experimental autoimmune encephalomyelitis.

Sci Rep 2021 Apr 30;11(1):9369. Epub 2021 Apr 30.

Department of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.

Human papilloma virus (HPV) vaccine is currently the most effective prophylaxis to prevent cervical cancer. However, concerns regarding its potential severe adverse reactions have limited the vaccination rate. HPV vaccines have been determined to contain adjuvants which induce inflammation by the innate immune system and are crucial for triggering adaptive immunity. Read More

View Article and Full-Text PDF

Pharmacological targeting of NLRP3 deubiquitination for treatment of NLRP3-associated inflammatory diseases.

Sci Immunol 2021 Apr;6(58)

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.

Pharmacologically inhibiting nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome activation results in potent therapeutic effects in a wide variety of preclinical inflammatory disease models. NLRP3 deubiquitination is essential for efficient NLRP3 inflammasome activity, but it remains unclear whether this process can be harnessed for therapeutic benefit. Here, we show that thiolutin (THL), an inhibitor of the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease, blocks NLRP3 inflammasome activation by canonical, noncanonical, alternative, and transcription-independent pathways at nanomolar concentrations. Read More

View Article and Full-Text PDF

Experimental Autoimmune Encephalomyelitis.

Clara Ballerini

Methods Mol Biol 2021 ;2285:375-384

Laboratory of Neuroimmunology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Experimental autoimmune encephalomyelitis, originally experimental allergic encephalomyelitis, is the well-known animal model of multiple sclerosis, an immune- mediated, demyelinating, inflammatory chronic disease of the central nervous system. The experimental disease is widely utilized to test new therapies in preclinical studies, to investigate new hypothesis on the possible pathogenic mechanisms of autoimmune reaction directed against the central nervous system or more generally to investigate the interactions between the immune system and the central nervous system that lead to neuroinflammation. The experimental autoimmune encephalomyelitis may be induced following different protocols in mammals, including nonhuman primates, and autoreactive CD4+ T-lymphocytes directed against myelin antigens are the main factors. Read More

View Article and Full-Text PDF
January 2021

Baricitinib Ameliorates Experimental Autoimmune Encephalomyelitis by Modulating the Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathway.

Front Immunol 2021 13;12:650708. Epub 2021 Apr 13.

Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) and a CD4+ T cell-mediated autoimmune disease. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is recognized as the major mechanism that regulates the differentiation and function of T helper (Th) 1 and Th17 cells, which are recognized as pivotal effector cells responsible for the development of EAE. We used baricitinib, a JAK 1/2 inhibitor, to investigate the therapeutic efficacy of inhibiting the JAK/STAT pathway in EAE mice. Read More

View Article and Full-Text PDF

A Soluble Epoxide Hydrolase Inhibitor, 1-TrifluoromethoxyPhenyl-3-(1-Propionylpiperidin-4-yl) Urea, Ameliorates Experimental Autoimmune Encephalomyelitis.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.

Polyunsaturated fatty acids (PUFAs) are essential FAs for human health. Cytochrome P450 oxygenates PUFAs to produce anti-inflammatory and pain-resolving epoxy fatty acids (EpFAs) and other oxylipins whose epoxide ring is opened by the soluble epoxide hydrolase (sEH/), resulting in the formation of toxic and pro-inflammatory vicinal diols (dihydroxy-FAs). Pharmacological inhibition of sEH is a promising strategy for the treatment of pain, inflammation, cardiovascular diseases, and other conditions. Read More

View Article and Full-Text PDF

FGF/FGFR Pathways in Multiple Sclerosis and in Its Disease Models.

Cells 2021 Apr 13;10(4). Epub 2021 Apr 13.

Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS) affecting more than two million people worldwide. In MS, oligodendrocytes and myelin sheaths are destroyed by autoimmune-mediated inflammation, while remyelination is impaired. Recent investigations of post-mortem tissue suggest that Fibroblast growth factor (FGF) signaling may regulate inflammation and myelination in MS. Read More

View Article and Full-Text PDF

Citicoline: A Candidate for Adjunct Treatment of Multiple Sclerosis.

Pharmaceuticals (Basel) 2021 Apr 2;14(4). Epub 2021 Apr 2.

Department of Neurology, Medical University of Lublin, 20-954 Lublin, Poland.

In remitting-relapsing multiple sclerosis (RR-MS), relapses are driven by autoreactive immune cells that enter the brain and spinal cord and damage myelin sheaths of axons in white and grey matter, whereas during remissions myelin is repaired by activated oligodendroglial cells. Disease-modifying therapies (DMTs) may either retard/attenuate myelin damage or promote/enhance/speed up myelin repair. Almost all currently approved DMTs inhibit myelin damage and are considerably toxic. Read More

View Article and Full-Text PDF

Increase in Autoantibodies-Abzymes with Peroxidase and Oxidoreductase Activities in Experimental Autoimmune Encephalomyelitis Mice during the Development of EAE Pathology.

Molecules 2021 Apr 4;26(7). Epub 2021 Apr 4.

Institute of Chemical Biology and Fundamental Medicine, SB of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.

The exact mechanisms of multiple sclerosis (MS) development are still unknown, but the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice is associated with the violation of bone marrow hematopoietic stem cells (HSCs) differentiation profiles associated with the production of harmful for human's autoantibodies hydrolyzing myelin basic protein, myelin oligodendrocyte glycoprotein (MOG), and DNA. It was shown that IgGs from the sera of healthy humans and autoimmune patients oxidize many different compounds due to their HO-dependent peroxidase and oxidoreductase activity in the absence of HO. Here we first analyzed the change in the relative redox activities of IgGs antibodies from the blood of C57BL/6 mice over time at different stages of the EAE development. Read More

View Article and Full-Text PDF

Illumination of Molecular Pathways in Multiple Sclerosis Lesions and the Immune Mechanism of Matrine Treatment in EAE, a Mouse Model of MS.

Front Immunol 2021 12;12:640778. Epub 2021 Apr 12.

Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

The etiology of multiple sclerosis (MS) is not clear, and the treatment of MS presents a great challenge. This study aimed to investigate the pathogenesis and potential therapeutic targets of MS and to define target genes of matrine, a quinolizidine alkaloid component derived from the root of that effectively suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To this end, the GSE108000 gene data set in the Gene Expression Omnibus Database, which included 7 chronic active MS lesions and 10 control samples of white matter, was analyzed for differentially expressed genes (DEGs). Read More

View Article and Full-Text PDF

ADAM9 enhances Th17 cell differentiation and autoimmunity by activating TGF-β1.

Proc Natl Acad Sci U S A 2021 May;118(18)

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215;

The a disintegrin and metalloproteinase (ADAM) family of proteinases alter the extracellular environment and are involved in the development of T cells and autoimmunity. The role of ADAM family members in Th17 cell differentiation is unknown. We identified ADAM9 to be specifically expressed and to promote Th17 differentiation. Read More

View Article and Full-Text PDF

Modeling compartmentalized chronic immune-mediated demyelinating CNS disease in the Biozzi ABH mouse.

J Neuroimmunol 2021 Apr 21;356:577582. Epub 2021 Apr 21.

Faculty of Medicine, Hebrew University of Jerusalem, Israel; The Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah - Hebrew University Medical Center, Jerusalem, Israel. Electronic address:

We explored whether experimental autoimmune encephalomyelitis (EAE) in Biozzi mice recapitulates temporal dynamics of tissue injury, immune-pathogenesis and CNS compartmentalization occurring in progressive multiple sclerosis (MS). Chronic EAE exhibited relapsing and progressing disease, partial closure of BBB, reduced tissue inflammatory activity, and development of meningeal ectopic lymphoid tissue, directly opposing (potentially driving) spinal subpial demyelinated plaques. A T cell predominant disease during relapses transformed into a B cell predominant disease in late chronic EAE, with high serum anti-MOG reactivity. Read More

View Article and Full-Text PDF

Astrocyte-specific expression of interleukin 23 leads to an aggravated phenotype and enhanced inflammatory response with B cell accumulation in the EAE model.

J Neuroinflammation 2021 Apr 27;18(1):101. Epub 2021 Apr 27.

Department of Neurology, University Clinic Bonn, Campus Venusberg 1, D-53127, Bonn, Germany.

Background: Interleukin 23 is a critical cytokine in the pathogenesis of multiple sclerosis. But the local impact of interleukin 23 on the course of neuroinflammation is still not well defined. To further characterize the effect of interleukin 23 on CNS inflammation, we recently described a transgenic mouse model with astrocyte-specific expression of interleukin 23 (GF-IL23 mice). Read More

View Article and Full-Text PDF

Neuroprotective effects of disubstituted dithiolethione ACDT against manganese-induced toxicity in SH-SY5Y cells.

Neurochem Int 2021 Apr 24;147:105052. Epub 2021 Apr 24.

Department of Pharmaceutical Sciences, MCPHS University, School of Pharmacy, 179 Longwood Avenue, Boston, MA, 02115, USA.

Dithiolethiones are lipophilic, organosulfur compounds that activate the Nrf2 transcription factor causing an upregulation of various phase II antioxidant enzymes. A disubstituted dithiolethione 5-amino-3-thioxo-3H-(1,2) dithiole-4-carboxylic acid ethyl ester (ACDT) retains the functional pharmacophore while also containing modifiable functional groups. Neuroprotection against autoimmune encephalomyelitis in vivo and 6-hydroxy dopamine (a model for Parkinson's disease) in vitro have been previously reported with ACDT. Read More

View Article and Full-Text PDF

Neuroimaging Patterns in Patients with COVID-19-Associated Neurological Complications: A Review.

Neurol India 2021 Mar-Apr;69(2):260-271

Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India.

Background: A variety of neuroimaging abnormalities in COVID-19 have been described.

Objectives: In this article, we reviewed the varied neuroimaging patterns in patients with COVID-19-associated neurological complications.

Methods: We searched PubMed, Google Scholar, Scopus and preprint databases (medRxiv and bioRxiv). Read More

View Article and Full-Text PDF

Testicular steroidogenesis is suppressed during experimental autoimmune encephalomyelitis in rats.

Sci Rep 2021 Apr 26;11(1):8996. Epub 2021 Apr 26.

Department for Neurobiology, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000, Belgrade, Serbia.

Multiple sclerosis (MS) is an autoimmune disease that usually occurs during the reproductive years in both sexes. Many male patients with MS show lower blood testosterone levels, which was also observed in male rats during experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To better understand the causes of decreased testosterone production during EAE, we investigated the expression status of genes and proteins associated with steroidogenesis in the testes. Read More

View Article and Full-Text PDF

Suppression of neuroinflammation by an allosteric agonist and positive allosteric modulator of the α7 nicotinic acetylcholine receptor GAT107.

J Neuroinflammation 2021 Apr 26;18(1):99. Epub 2021 Apr 26.

Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital and Hebrew University Medical School, Jerusalem, Israel.

Background: The α7 nicotinic acetylcholine receptor (α7 nAChR) negatively regulates the synthesis and release of pro-inflammatory cytokines by immune cells. Our previous studies showed that in encephalitogenic T cells, α7 nAChR expression is upregulated and that activation of the cholinergic system can attenuate experimental autoimmune encephalomyelitis (EAE). GAT107 is an allosteric agonist and positive allosteric modulator (ago-PAM) of α7 nAChR that can produce persistent activation of this receptor. Read More

View Article and Full-Text PDF