T Helper Cells: The Modulators of Inflammation in Multiple Sclerosis

Cells, Journal Year: 2020, Volume and Issue: 9(2), P. 482 - 482

Published: Feb. 19, 2020

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by the progressive loss of axonal myelin in several areas central nervous system (CNS) that responsible for clinical symptoms such as muscle spasms, optic neuritis, and paralysis. The progress made more than one decade research animal models MS clarifying pathophysiology validated concept an autoimmune inflammatory disorder caused recruitment CNS self-reactive lymphocytes, mainly CD4+ T cells. Indeed, high levels helper (Th) cells related cytokines chemokines have been found lesions cerebrospinal fluid (CSF) patients, thus contributing to breakdown blood–brain barrier (BBB), activation resident astrocytes microglia, finally outcome neuroinflammation. To date, types Th discovered designated according secreted lineage-defining cytokines. Interestingly, Th1, Th17, Th1-like Th9, Th22 associated with MS. In this review, we discuss role interplay different cell subpopulations their modulating responses approved well novel therapeutic approaches targeting lymphocytes treatment disease.

Language: Английский

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The Role of Natural Killer Cells in Autoimmune Diseases

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 25, 2021

Natural killer (NK) cells, the large granular lymphocytes differentiated from common lymphoid progenitors, were discovered in early 1970's. They are members of innate immunity and initially defined by their strong cytotoxicity against virus-infected cells important effector functions anti-tumoral immune responses. Nowadays, NK classified among recently cell subsets have capacity to influence both adaptive Therefore, they can be considered as that stands between arms immunity. don't express T or B receptors recognized absence CD3. There two major subgroups according differential expression CD16 CD56. While

Language: Английский

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Oral Administration of miR-30d from Feces of MS Patients Suppresses MS-like Symptoms in Mice by Expanding Akkermansia muciniphila

Cell Host & Microbe, Journal Year: 2019, Volume and Issue: 26(6), P. 779 - 794.e8

Published: Nov. 26, 2019

Language: Английский

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Metabolic Control of Astrocyte Pathogenic Activity via cPLA2-MAVS

Cell, Journal Year: 2019, Volume and Issue: 179(7), P. 1483 - 1498.e22

Published: Dec. 1, 2019

Language: Английский

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Fate-Mapping of GM-CSF Expression Identifies a Discrete Subset of Inflammation-Driving T Helper Cells Regulated by Cytokines IL-23 and IL-1β

Immunity, Journal Year: 2019, Volume and Issue: 50(5), P. 1289 - 1304.e6

Published: May 1, 2019

Language: Английский

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Detrimental and protective action of microglial extracellular vesicles on myelin lesions: astrocyte involvement in remyelination failure

Acta Neuropathologica, Journal Year: 2019, Volume and Issue: 138(6), P. 987 - 1012

Published: July 30, 2019

Microglia are highly plastic immune cells which exist in a continuum of activation states. By shaping the function oligodendrocyte precursor (OPCs), brain differentiate to myelin-forming cells, microglia participate both myelin injury and remyelination during multiple sclerosis. However, mode(s) action supporting or inhibiting repair is still largely unclear. Here, we analysed effects extracellular vesicles (EVs) produced vitro by either pro-inflammatory pro-regenerative on OPCs at demyelinated lesions caused lysolecithin injection mouse corpus callosum. Immunolabelling for proteins electron microscopy showed that EVs released blocked remyelination, whereas co-cultured with immunosuppressive mesenchymal stem promoted OPC recruitment repair. The molecular mechanisms responsible harmful beneficial EV actions were dissected primary cultures. exposing OPCs, cultured alone astrocytes, inflammatory EVs, observed blockade maturation only presence implicating these failure. Biochemical fractionation revealed astrocytes may be converted into cargo, as indicated immunohistochemical qPCR analyses, surface lipid components promote migration and/or differentiation, linking lipids Although through species enhance remain fully defined, provide first demonstration vesicular sphingosine 1 phosphate stimulates migration, fundamental step From this study, microglial emerge multimodal multitarget signalling mediators able influence around lesions, exploited develop novel approaches not sclerosis, but also neurological neuropsychiatric diseases characterized demyelination.

Language: Английский

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Cellular immunology of relapsing multiple sclerosis: interactions, checks, and balances

The Lancet Neurology, Journal Year: 2021, Volume and Issue: 20(6), P. 470 - 483

Published: April 27, 2021

Language: Английский

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Neuropathobiology of COVID-19: The Role for Glia

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Nov. 11, 2020

SARS-CoV-2, which causes the Coronavirus Disease 2019 (COVID-19) pandemic, has a strong brain neurotropism via binding to receptor angiotensin-converting enzyme 2 expressed by neurones and glial cells, including astrocytes microglia. Systemic infection accompanies severe cases of COVID-19 also triggers substantial increase in circulating levels chemokines interleukins that compromise blood-brain barrier, enter parenchyma affect its defensive systems, Brain areas devoid barrier such as circumventricular organs are particularly vulnerable inflammatory mediators. The performance microglia, well immune cells required for health, is considered critical defining neurological damage outcome COVID-19. In this review, we discuss implication neuroinflammation, adaptive innate immunity, autoimmunity, astrocytic microglial homeostatic functions psychiatric aspects consequences SARS-CoV-2 during ageing, presence systemic comorbidities, exposed pregnant mother foetus will be specifically covered.

Language: Английский

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Brain expression quantitative trait locus and network analyses reveal downstream effects and putative drivers for brain-related diseases

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(3), P. 377 - 388

Published: Feb. 23, 2023

Identification of therapeutic targets from genome-wide association studies (GWAS) requires insights into downstream functional consequences. We harmonized 8,613 RNA-sequencing samples 14 brain datasets to create the MetaBrain resource and performed cis- trans-expression quantitative trait locus (eQTL) meta-analyses in multiple region- ancestry-specific (n ≤ 2,759). Many 16,169 cortex cis-eQTLs were tissue-dependent when compared with blood cis-eQTLs. inferred cell types for 3,549 by interaction analysis. prioritized 186 31 brain-related traits using Mendelian randomization co-localization including 40 an type, such as a neuron-specific cis-eQTL (CYP24A1) sclerosis. further describe 737 trans-eQTLs 526 unique variants 108 genes. used brain-specific gene-co-regulation networks link GWAS loci prioritize additional genes five central nervous system diseases. This study represents valuable post-GWAS research on

Language: Английский

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Alterations in Circulating Fatty Acid Are Associated With Gut Microbiota Dysbiosis and Inflammation in Multiple Sclerosis

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: July 7, 2020

Background: Butyric acid (BA) is a short-chain fatty (SCFA) with anti-inflammatory properties, which promotes intestinal barrier function. Medium-chain acids (MCFA), including caproic (CA), promote TH1 and TH17 differentiation, thus supporting inflammation. Aim: Since most SCFAs are absorbed in the cecum colon, measurement of BA peripheral blood could provide information on health status ecosystem. Additionally, given different immunomodulatory properties CA evaluation their serum concentration, as well ratio be simple rapid biomarker disease activity and/or treatment efficacy MS. Methods: We evaluated concentrations, immune parameters, integrity gut microbiota composition patients multiple sclerosis (MS) comparing result to those obtained healthy controls. Results: In MS, concentration was reduced that increased. Concurrently, depleted producers while it enriched mucin-degrading, pro-inflammatory components. The seen MS correlated alterations permeability, evidenced by higher plasma concentrations lipopolysaccharide acid-binding protein, Specifically, positively associated CD4+/IFN+ T lymphocytes, BA/CA CD4+/CD25high/Foxp3+ negatively lymphocytes. Conclusion: dysbiosis found results SCFA/MCFA barrier; this explain chronic inflammation characterizes disease. SCFA MCFA quantification evaluate therapeutic rehabilitation procedures

Language: Английский

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