scholarly journals Interactions between Neutrophils, Th17 Cells, and Chemokines during the Initiation of Experimental Model of Multiple Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Dagmara Weronika Wojkowska ◽  
Piotr Szpakowski ◽  
Dominika Ksiazek-Winiarek ◽  
Marcin Leszczynski ◽  
Andrzej Glabinski
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Th17 Cells ◽  
Inflammatory Cell ◽  
Autoimmune Encephalomyelitis ◽  
Preclinical Phase ◽  
Activated T Cell ◽  
Cell Subpopulations ◽  
The Brain ◽  
Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) in which activated T cell and neutrophil interactions lead to neuroinflammation. In this study the expression of CCR6, CXCR2, and CXCR6 in Th17 cells and neutrophils migrating to the brain during EAE was measured, alongside an evaluation of the production of IL-17, IL-23, CCL-20, and CXCL16 in the brain. Next, inflammatory cell subpopulations accumulating in the brain after intracerebral injections of IL-17 or CXCL1, as well as during modulation of EAE with anti-IL-23R or anti-CXCR2 antibodies, were analyzed. Th17 cells upregulate CXCR2 during the preclinical phase of EAE and a significant migration of these cells to the brain was observed. Neutrophils upregulated CCR6, CXCR2, and CXCR6 during EAE, accumulating in the brain both prior to and during acute EAE attacks. Production of IL-17, IL-23, CCL20, and CXCL16 in the CNS was increased during both preclinical and acute EAE. Intracerebral delivery of CXCL1 stimulated the early accumulation of neutrophils in normal and preclinical EAE brains but reduced the migration of Th17 cells to the brain during the preclinical stage of EAE. Modulation of EAE by anti-IL-23R antibodies ameliorated EAE by decreasing the intracerebral accumulation of Th17 cells.

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.

scholarly journals The direct deleterious effect of Th17 cells in the nervous system compartment in multiple sclerosis and experimental autoimmune encephalomyelitis: one possible link between neuroinflammation and neurodegeneration

2020 ◽  
Vol 28 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Rodica Balasa ◽  
Smaranda Maier ◽  
Laura Barcutean ◽  
Adina Stoian ◽  
Anca Motataianu
Keyword(s):  
Multiple Sclerosis ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cells ◽  
Direct Interaction ◽  
Autoimmune Encephalomyelitis ◽  
Cns Inflammation ◽  
Direct Role ◽  
Autoimmune Attack ◽  
Experimental Autoimmune

AbstractThe processes of demyelination and neurodegeneration in the central nervous system (CNS) of multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE) are secondary to numerous pathophysiological mechanisms. One of the main cellular players is the Th17 lymphocyte. One of the major functions described for Th17 cells is the upregulation of pro-inflammatory cytokines, such as IL-17 at the level of peripheral and CNS inflammation. This review will focus on the newly described and unexpected, direct role played by the Th17 cells in the CNS of MS patients and EAE models. Th17 and their main cytokine, IL-17, are actively involved in the onset and maintenance of the immune cascade in the CNS compartment as Th17 were found to achieve brain-homing potential. Direct interaction of myelin oligodendrocyte glycoprotein - specific Th17 with the neuronal cells firstly induces demyelination and secondly, extensive axonal damage. The Th17 cells promote an inflammatory B cell response beyond the BBB through the presence of infiltrating Th follicles. Due to their role in preventing remyelination and direct neurotoxic effect, Th17 cells might stand for an important connection between neuroinflammation and neurodegeneration in a devastating disease like MS. The Th17 cell populations have different mechanisms of provoking an autoimmune attack not only in the periphery but also in the CNS of MS patients.

scholarly journals Environmental enrichment alleviates the deleterious effects of stress in experimental autoimmune encephalomyelitis

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732095980
Author(s):  
Antoine Philippe Fournier ◽  
Erwan Baudron ◽  
Isabelle Wagnon ◽  
Philippe Aubert ◽  
Denis Vivien ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Environmental Enrichment ◽  
Acute Stress ◽  
Stressful Events ◽  
Autoimmune Encephalomyelitis ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Experimental Autoimmune

Background Clinical observations support the hypothesis that stressful events increase relapse occurrence in multiple sclerosis patients, while stress-reduction strategies can modulate this effect. However, a direct cause-effect relationship between stress level and relapse cannot be firmly established from these data. Objectives The purpose of this work was to address whether modulation of stress could interfere with symptom relapse in an animal model of multiple sclerosis with relapsing-remitting course. Methods Mice bred in standard or enriched environment were subjected to repeated acute stress during the remission phase of relapsing-remitting PLP-induced experimental autoimmune encephalomyelitis. Results We report that repeated acute stress induced a twofold increase in relapse incidence in experimental autoimmune encephalomyelitis. On the other hand, environmental enrichment reduced relapse incidence and severity, and reversed the effects of repeated acute stress. Conclusion These data provide the platform for further studies on the biological processes that link stress and multiple sclerosis relapses in a suitable animal model.

Mesenchymal stem cells as a treatment for multiple sclerosis: a focus on experimental animal studies

2020 ◽  
Vol 31 (2) ◽  
pp. 161-179 ◽  
Author(s):  
Ahmed Lotfy ◽  
Nourhan S. Ali ◽  
Mai Abdelgawad ◽  
Mohamed Salama
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Animal Studies ◽  
Culture Medium ◽  
Therapeutic Effects ◽  
Autoimmune Encephalomyelitis ◽  
Main Factors ◽  
Experimental Autoimmune

AbstractMultiple sclerosis (MS) is a progressive and debilitating neurological condition in which the immune system abnormally attacks the myelin sheath insulating the nerves. Mesenchymal stem cells (MSCs) are found in most adult tissues and play a significant systemic role in self-repair. MSCs have promising therapeutic effects in many diseases, such as autoimmune diseases, including MS. MSCs have been tested in MS animal models, such as experimental autoimmune encephalomyelitis. Other studies have combined other agents with MSCs, genetically modified MSCs, or used culture medium from MSCs. In this review, we will summarize these studies and compare the main factors in each study, such as the source of MSCs, the type of animal model, the route of injection, the number of injected cells, and the mechanism of action.

scholarly journals Myelin Basic Protein–specific T Helper 2 (Th2) Cells Cause Experimental Autoimmune Encephalomyelitis in Immunodeficient Hosts Rather than Protect Them from the Disease

1997 ◽  
Vol 186 (2) ◽  
pp. 307-312 ◽  
Author(s):  
Juan J. Lafaille ◽  
Fabienne Van de Keere ◽  
Albert L. Hsu ◽  
Jody L. Baron ◽  
Werner Haas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Basic Protein ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Autoimmune Encephalomyelitis ◽  
Preclinical Phase ◽  
Deficient Mice ◽  
Th1 And Th2 ◽  
Experimental Autoimmune

Chronic inflammatory autoimmune diseases such as multiple sclerosis, diabetes, and rheumatoid arthritis are caused by CD4+ Th1 cells. Because Th2 cells antagonize Th1 cell functions in several ways, it is believed that immune deviation towards Th2 can prevent or cure autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease used as a model for multiple sclerosis. Using an adoptive transfer system we assessed the role of Th1 and Th2 cells in EAE. In vitro generated Th1 and Th2 cells from myelin basic protein (MBP)-specific TCR transgenic mice were transferred into normal and immunodeficient mice. Th1 cells caused EAE in all recipients after a brief preclinical phase. Surprisingly, Th2 cells also caused EAE in RAG-1 KO mice and in αβ T cell–deficient mice, albeit after a longer preclinical phase. Normal or γδ T cell–deficient mice were resistant to EAE induced by Th2 cells. The histopathological features of this disease resembled those of an allergic process. In addition, disease induction by Th1 cells was not altered by coadmininstration of Th2 cells in any of the recipients. These findings indicate that MBP-specific Th2 cells have the potential to induce EAE and that the disease induced by previously activated Th1 cells cannot be prevented by normal lymphocytes nor by previously activated Th2 cells.

MDC/CCL22 intrathecal levels in patients with multiple sclerosis

2008 ◽  
Vol 14 (4) ◽  
pp. 547-549 ◽  
Author(s):  
D. Galimberti ◽  
C. Fenoglio ◽  
C. Comi ◽  
D. Scalabrini ◽  
M. De Riz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Th2 Cells ◽  
Autoimmune Encephalomyelitis ◽  
Disease Subtype ◽  
Male Patients ◽  
Fluid Levels ◽  
The Brain ◽  
Experimental Autoimmune

MDC/CCL22 has been detected in the brain of mice with experimental autoimmune encephalomyelitis. MDC/CCL22 cerebrospinal fluid levels were evaluated in 56 patients with multiple sclerosis (MS) and in 17 controls. No significant differences were found, even when stratifying patients according to the disease subtype. Stratifying by gender, significantly increased MDC/CCL22 levels were observed in female patients when compared with female controls and male patients (109.03 versus 98.54 and 99.37 pg/mL, P = 0.034 and 0.018, respectively). Therefore, MDC/CCL22 is likely to play a role in the development of MS in females only, possibly influencing the intracerebral recruitment of Th2 cells, which produce anti-inflammatory cytokines. Multiple Sclerosis 2008; 14: 547—549. http://msj.sagepub.com

scholarly journals Commentary: The Impact of Regional Astrocyte Interferon- Signaling During Chronic Autoimmunity: A Novel Role for the Immunoproteasome

2021 ◽  
Vol 5 (1) ◽  
pp. 6-9
Author(s):  
Brandon Smith ◽  
Jessica Williams
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Treatment Strategies ◽  
Mechanisms Of Action ◽  
Interferon Signaling ◽  
Autoimmune Encephalomyelitis ◽  
Disease States ◽  
Therapeutic Development ◽  
The Impact ◽  
Experimental Autoimmune

Despite an increase in approved therapies for treating the inflammatory and neurodegenerative disease multiple sclerosis (MS), many of which have efficacy in the early, acute phases, there are no reliable treatments for the chronic, progressive stages of the disease. A deeper understanding of the biological underpinnings that govern differences between acute and chronic stages of MS and an animal model of MS, experimental autoimmune encephalomyelitis, will inform therapeutic development and personalized treatment strategies. It is well-known that the effects of inflammation are complex and the implications vary between stages. Complimentary to our recent publication, we will discuss here the pleiotropic effects of the cytokine interferon across disease states, along with the implications of downstream mechanisms of action.

scholarly journals TPL2 mediates autoimmune inflammation through activation of the TAK1 axis of IL-17 signaling

2014 ◽  
Vol 211 (8) ◽  
pp. 1689-1702 ◽  
Author(s):  
Yichuan Xiao ◽  
Jin Jin ◽  
Mikyoung Chang ◽  
Mako Nakaya ◽  
Hongbo Hu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cells ◽  
Autoimmune Encephalomyelitis ◽  
Signaling Mechanism ◽  
Catalytic Activation ◽  
Autoimmune Inflammation ◽  
Receptor Signal ◽  
Inflammatory Action ◽  
Experimental Autoimmune

Development of autoimmune diseases, such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), involves the inflammatory action of Th1 and Th17 cells, but the underlying signaling mechanism is incompletely understood. We show that the kinase TPL2 is a crucial mediator of EAE and is required for the pathological action of Th17 cells. TPL2 serves as a master kinase mediating the activation of multiple downstream pathways stimulated by the Th17 signature cytokine IL-17. TPL2 acts by linking the IL-17 receptor signal to the activation of TAK1, which involves a dynamic mechanism of TPL2–TAK1 interaction and TPL2-mediated phosphorylation and catalytic activation of TAK1. These results suggest that TPL2 mediates TAK1 axis of IL-17 signaling, thereby promoting autoimmune neuroinflammation.

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