Mesenchymal stromal cells attenuate multiple sclerosis via IDO-dependent increasing the suppressive proportion of CD5+ IL-10+ B cells.

In this study, we analyzed the phenotypic feature of peripheral blood mononuclear cells (PBMCs) in MS patients and found that the patients exhibited an increase in the frequency of B cells, but a markedly decrease in frequency of CD5+ and IL-10+ B cells compared to healthy controls. Infusion of MSCs exhibited a significant therapeutic effect on the experimental autoimmune encephalomyelitis (EAE) mice, infiltration of mononuclear cells and demyelination of the spinal cords were both reduced in CNS of the mice, the frequency of CD5+ IL-10+ B cells in the mice was significantly increased. Additionally, when PBMCs or B cells from MS patients were co-cultured with MSCs, the frequency of CD5+ IL-10+ B cells also increased, the proliferative and immunosuppressive capacity of CD5+ B cells were significantly enhanced while the apoptosis ratio of this cellular subset significantly decreased. Moreover, those effects could be eliminated while the indoleamine 2,3-dioxygenase (IDO) inhibitor, D/L-1MT, was added to the co-cultured cells. In summary, this study suggests that MSCs can control EAE via IDO pathway to promote the proportion and function of CD5+ IL-10+ B cells, providing a promise to treat patients with MS in the clinical setting. PMID: 31632539 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research

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Authors: Kamal A, Hosny M, Abd Elwahab A, Shawki Kamal Y, Shehata HS, Hassan A Abstract BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). Aberrant expression of transcription factor forkhead box P3 (FoxP3) has been suggested to underlie different immunological disorders as FOXP3 expression is essential for T regulatory cells (Tregs) to maintain their suppressive and anti-inflammatory functions and exert immunologic self-tolerance. Interleukin-35 (IL-35) is an important immunosuppressive cytokine that is produced mainly by CD4+ FOXP3+ Tregs. OBJECTIVES: To a...
Source: Revue Neurologique - Category: Neurology Tags: Rev Neurol (Paris) Source Type: research
Abstract Multiple sclerosis is a chronic inflammatory demyelinating disorder of the central nervous system that eventually leads to progressive neurodegeneration and disability. Recent findings highlighted the emerging role of each target of the endocannabinoid system in controlling the symptoms and disease progression of multiple sclerosis. Therefore, multi-target modulators of the endocannabinoid system could provide a more effective pharmacological strategy as compared to the single target modulation. In this work, N-cycloheptyl-1,2-dihydro-5-bromo-1-(4-fluorobenzyl)-6-methyl-2-oxo-pyridine-3-carboxamide (B2) w...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research
Abstract BACKGROUND: The human myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (huMOG-EAE) model, generates B-cell driven demyelination in mice, making it a suitable multiple sclerosis model to study B cell depletion. OBJECTIVES: We investigated the effect of subcutaneous anti-CD20 antibody treatment on huMOG-EAE gray matter (GM) pathology. METHODS: C57Bl/6, 8-week old mice were immunized with 200 huMOG1-125 and treated with 50 μg/mouse of anti-CD20 antibody (n = 16) or isotype control (n = 16). Serial brain volumetric 9.4 T MRI scans was performed at ...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
Conclusions: Ferritin deficiency in MS patients is associated with an exacerbation of depressive disorders and a decline in quality of life. Symptoms of fatigue in MS patients are inversely proportional to mood and quality of life.
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
CONCLUSIONS: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients. PMID: 32964823 [PubMed - as supplied by publisher]
Source: Current Drug Discovery Technologies - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Discov Technol Source Type: research
Basel, 10 September 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) will present new ENSPRYNG ® (satralizumab) data on reducing relapse severity in the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare disease of the central nervous system. These data are being presented at MSVirtual2020, the 8th joint ACTRIMS-ECTRIMS meeting, in addition to longer-term efficacy data supporting the continued effect of ENSPRYNG on reducing the risk of NMOSD relapse, as well as its favourable benefit:risk profile.“The data for ENSPRYNG at MSVirtual2020 are promising and suggest it significantly reduces relapse severity ...
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
Multiple sclerosis (MS), an autoimmune disease of the central nervous system, generally starts as the relapsing remitting form (RRMS), but often shifts into secondary progressive MS (SPMS). SPMS represents a more advanced stage of MS, characterized by accumulating disabilities and refractoriness to medications. The aim of this study was to...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: Biological Sciences Source Type: research
Conclusions: These data suggest that combined intravenous and intrathecal low-dose hUC-MSCs transplantation is safe and feasible in RRMS and NMO patients in the long term. The conclusion requires confirmation by future clinical trials in a larger cohort.
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Comorbidities in patients with multiple sclerosis (MS) has become an area of increasing interest in the recent years. A comorbidity is defined as any additional disease that coexists in an individual with a given index disease and that is not an obvious complication of the index disease. The aim of this review is to describe the current evidence regarding the range of comorbidities in the population with MS reported in different countries and the current knowledge about the influence of comorbidities on the clinical features and therapeutic challenges in MS. Certain comorbidities are more prevalent in people with MS such a...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
The most prominent pathological features of multiple sclerosis (MS) are demyelination and neurodegeneration. The exact pathogenesis of MS is unknown, but it is generally regarded as a T cell-mediated autoimmune disease. Increasing evidence, however, suggests that other components of the immune system, particularly B cells and antibodies, contribute to the cumulative CNS damage and worsening disability that characterize the disease course in many patients. We have previously described strongly elevated T cell reactivity to an extracellular domain of the most abundant CNS myelin protein, myelin proteolipid protein (PLP) in p...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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