scholarly journals Pericytes as mediators of infiltration of macrophages in multiple sclerosis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Deepak Kumar Kaushik ◽  
Anindita Bhattacharya ◽  
Brian Mark Lozinski ◽  
V. Wee Yong
Keyword(s):  
Multiple Sclerosis ◽  
Critical Role ◽  
Neurovascular Unit ◽  
Immunohistochemical Analysis ◽  
Matrix Proteins ◽  
Autoimmune Encephalomyelitis ◽  
Mural Cells ◽  
Inflammatory Chemokines ◽  
The Central Nervous System

Abstract Background Multiple sclerosis (MS) is a neurodegenerative condition of the central nervous system (CNS). It is associated with blood–brain barrier (BBB) breakdown and intravasation of leukocytes, particularly monocyte-derived macrophages, into the CNS. Pericytes are mural cells that are encased within the basement membrane of vasculature, and they contribute functionally to the neurovascular unit. These cells play an important role in maintaining BBB integrity and CNS homeostasis. However, the critical role of pericytes in mediating inflammation in MS or its models is unclear. Whether pericytes infiltrate into the CNS parenchyma in MS also needs clarification. Methods CNS samples from the experimental autoimmune encephalomyelitis (EAE) mouse model of MS were collected at different time points for immunohistochemical analysis of pericytes along the inflamed vasculature. These findings were validated using MS brain specimens, and further analysis of pericyte involvement in inflammation was carried out by culturing primary pericytes and macrophages. Multiplex ELISA, transmigration assay and real-time PCR were used to study the inflammatory potential of pericytes in cultures. Results We found that pericytes exhibit a heterogenous morphology, with notable elongation in the inflamed perivascular cuffs of EAE. This was manifested by a decrease in pericyte density but an increase in the coverage by pericytes along the vasculature. Chondroitin sulfate proteoglycans (CSPGs), a family of extracellular matrix proteins enriched within inflamed perivascular cuffs, elevated levels of pro-inflammatory chemokines/cytokines in pericytes in culture. Importantly, pericytes stimulated with CSPGs enhanced macrophage migration. We did not detect pericytes in the CNS parenchyma during EAE, and this was corroborated in MS brain samples. Conclusions Our data suggest that pericytes seek to restore the BBB through increased coverage, but that their exposure to CSPGs prompt their facilitation of macrophages to enter the CNS to elevate neuroinflammation in EAE and MS.

scholarly journals Role of Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2020 ◽  
Author(s):  
Sarah Dhaiban ◽  
Mena Al-Ani ◽  
Noha Mousaad Elemam ◽  
Mahmood H Al-Aawad ◽  
Zeinab Al-Rawi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
T Regulatory Cells ◽  
Cell Types ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Chronic Autoimmune Disease ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by varying degrees of demyelination of uncertain etiology, and is associated with specific environmental and genetic factors. Upon recognition of CNS antigens, the immune cells initiate an inflammatory process which leads to destruction and deterioration of the neurons. Innate immune cells such as macrophages, dendritic cells and natural killer cells are known to play critical roles in the pathogenesis of MS. Also, the activation of peripheral CD4+ T cells by CNS antigens leads to their extravasation into the CNS causing damages that exacerbates the disease. This could be accompanied by dysregulation of T regulatory cells and other cell types functions. Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS disease. In this review, we highlight the roles of innate and adaptive immune players in the pathogenesis of MS and EAE.

The role of Toll-like receptors in multiple sclerosis and possible targeting for therapeutic purposes

2014 ◽  
Vol 0 (0) ◽  
Author(s):  
Maziar Gooshe ◽  
Amir Hossein Abdolghaffari ◽  
Maria Elsa Gambuzza ◽  
Nima Rezaei
Keyword(s):  
Multiple Sclerosis ◽  
Host Defense ◽  
Toll Like Receptors ◽  
Autoimmune Encephalomyelitis ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Chronic Autoimmune Disease ◽  
Ms Therapy ◽  
Experimental Autoimmune

AbstractThe interaction between the immune and nervous systems suggests invaluable mechanisms for several pathological conditions, especially neurodegenerative disorders. Multiple sclerosis (MS) is a potentially disabling chronic autoimmune disease, characterized by chronic inflammation and neurodegenerative pathology of the central nervous system. Toll-like receptors (TLRs) are an important family of receptors involved in host defense and in recognition of invading pathogens. The role of TLRs in the pathogenesis of autoimmune disorders such as MS is only starting to be uncovered. Recent studies suggest an ameliorative role of TLR3 and a detrimental role of other TLRs in the onset and progression of MS and experimental autoimmune encephalomyelitis, a murine model of MS. Thus, modulating TLRs can represent an innovative immunotherapeutic approach in MS therapy. This article outlines the role of these TLRs in MS, also discussing TLR-targeted agonist or antagonists that could be used in the different stages of the disease.

scholarly journals Multiple Sclerosis CD49d+CD154+ As Myelin-Specific Lymphocytes Induced During Remyelination

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 15
Author(s):  
Paweł Piatek ◽  
Magdalena Namiecinska ◽  
Małgorzata Domowicz ◽  
Marek Wieczorek ◽  
Sylwia Michlewska ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cumulative Effect ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Cns Demyelination ◽  
The Brain ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) mediated by autoreactive lymphocytes. The role of autoreactive lymphocytes in the CNS demyelination is well described, whereas very little is known about their role in remyelination during MS remission. In this study, we identified a new subpopulation of myelin-specific CD49d+CD154+ lymphocytes presented in the peripheral blood of MS patients during remission, that proliferated in vitro in response to myelin peptides. These lymphocytes possessed the unique ability to migrate towards maturing oligodendrocyte precursor cells (OPCs) and synthetize proinflammatory chemokines/cytokines. The co-culture of maturing OPCs with myelin-specific CD49d+CD154+ lymphocytes was characterized by the increase in proinflammatory chemokine/cytokine secretion that was not only a result of their cumulative effect of what OPCs and CD49d+CD154+ lymphocytes produced alone. Moreover, maturing OPCs exposed to exogenous myelin peptides managed to induce CD40-CD154-dependent CD49d+CD154+ lymphocyte proliferation. We confirmed, in vivo, the presence of CD49d+CD154+ cells close to maturating OPCs and remyelinating plaque during disease remission in the MS mouse model (C57Bl/6 mice immunized with MOG35-55) by immunohistochemistry. Three weeks after an acute phase of experimental autoimmune encephalomyelitis, CD49d+/CD154+ cells were found to be co-localized with O4+ cells (oligodendrocyte progenitors) in the areas of remyelination identified by myelin basic protein (MBP) labelling. These data suggested that myelin-specific CD49d+CD154+ lymphocytes present in the brain can interfere with remyelination mediated by oligodendrocytes probably as a result of establishing proinflammatory environment.

scholarly journals Therapeutic Targeting of Immune Cell Autophagy in Multiple Sclerosis: Russian Roulette or Silver Bullet?

2021 ◽  
Vol 12 ◽  
Author(s):  
Guan Yang ◽  
Luc Van Kaer
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Nerve Fibers ◽  
Therapeutic Approaches ◽  
Autoimmune Encephalomyelitis ◽  
Autoimmune And Inflammatory Diseases ◽  
The Central Nervous System

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) in which the immune system damages the protective insulation surrounding nerve fibers that project from neurons. The pathological hallmark of MS is multiple areas of myelin loss accompanied by inflammation within the CNS, resulting in loss of cognitive function that ultimately leads to paralysis. Recent studies in MS have focused on autophagy, a cellular self-eating process, as a potential target for MS treatment. Here, we review the contribution of immune cell autophagy to the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the prototypic animal model of MS. A better understanding of the role of autophagy in different immune cells to EAE might inform the development of novel therapeutic approaches in MS and other autoimmune and inflammatory diseases.

scholarly journals Role of the PD‐1/PD‐L1 Signaling in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Recent Insights and Future Directions

2021 ◽  
Author(s):  
Yan Mi ◽  
Jinming Han ◽  
Jie Zhu ◽  
Tao Jin
Keyword(s):  
Multiple Sclerosis ◽  
T Lymphocytes ◽  
Experimental Autoimmune Encephalomyelitis ◽  
B Lymphocytes ◽  
Immune Cells ◽  
Autoimmune Encephalomyelitis ◽  
Activated T Lymphocytes ◽  
The Central Nervous System ◽  
Experimental Autoimmune

AbstractMultiple sclerosis (MS) is an autoimmunity-related chronic demyelination disease of the central nervous system (CNS), causing young disability. Currently, highly specific immunotherapies for MS are still lacking. Programmed cell death 1 (PD-1) is an immunosuppressive co-stimulatory molecule, which is expressed on activated T lymphocytes, B lymphocytes, natural killer cells, and other immune cells. PD-L1, the ligand of PD-1, is expressed on T lymphocytes, B lymphocytes, dendritic cells, and macrophages. PD-1/PD-L1 delivers negative regulatory signals to immune cells, maintaining immune tolerance and inhibiting autoimmunity. This review comprehensively summarizes current insights into the role of PD-1/PD-L1 signaling in MS and its animal model experimental autoimmune encephalomyelitis (EAE). The potentiality of PD-1/PD-L1 as biomarkers or therapeutic targets for MS will also be discussed.

scholarly journals Potential Role of Trace Elements (Al, Cu, Zn, and Se) in Multiple Sclerosis Physiopathology

2020 ◽  
Vol 27 (4) ◽  
pp. 163-177
Author(s):  
Mohammad Sadegh Hesamian ◽  
Nahid Eskandari
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Trace Elements ◽  
Plasma Cells ◽  
Peripheral Tolerance ◽  
The Central Nervous System ◽  
Living Organisms ◽  
Tolerance Breakdown ◽  
Peripheral Immune Cells

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system. The cause of MS is not known completely, and pathology is specified by involved demyelinated areas in the white and gray matter of the brain and spinal cord. Inflammation and peripheral tolerance breakdown due to Treg cell defects and/or effector cell resistance are present at all stages of the disease. Several invading peripheral immune cells are included in the process of the disease such as macrophages, CD8+ T cells, CD4+ T cells, B cells, and plasma cells. Trace elements are known as elements found in soil, plants, and living organisms in small quantities. Some of them (e.g., Al, Cu, Zn, Mn, and Se) are essential for the body’s functions like catalysts in enzyme systems, energy metabolism, etc. Al toxicity and Cu, Zn, and Se toxicity and deficiency can affect the immune system and following neuron inflammation and degeneration. These processes may result in MS pathology. Of course, factors such as lifestyle, environment, and industrialization can affect levels of trace elements in the human body.

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

2021 ◽  
Author(s):  
William E. Barclay ◽  
M. Elizabeth Deerhake ◽  
Makoto Inoue ◽  
Toshiaki Nonaka ◽  
Kengo Nozaki ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Animal Model ◽  
Cell Death ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammasome Activation ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.SIGNIFICANCE STATEMENTInflammasome activation in the peripheral immune system is pathogenic in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, inflammasome activity in the central nervous system (CNS) is largely unexplored. Here, we used genetically modified mice to determine inflammasome activation in the CNS during EAE. Our data indicated heightened AIM2 inflammasome activation in astrocytes after the disease peak. Unexpectedly, neither CNS-infiltrated myeloid cells nor microglia were the primary cells with activated inflammasomes in SC during EAE. Despite AIM2 inflammasome activation, astrocytes did not undergo apparent cell death and produced little of the proinflammatory cytokine, IL-1β, during EAE. This study showed that CNS inflammasome activation occurs during EAE without associating with IL-1β-mediated inflammation.

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