scholarly journals Increase in MMP-9 Expressing CD11b+ cells in a CD44 Dependent Way Reduces Severity of Experimental Autoimmune Encephalomyelitis

2018 ◽  
Vol 14 (3) ◽  
pp. 147-149
Author(s):  
Sujata Kar ◽  
Kalipada Kar
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
Neurodegenerative Disorder ◽  
Cellular Adhesion ◽  
Phagocytic Cells ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Background: Multiple sclerosis (MS) is a dangerous neurodegenerative disorder. Various aspects of  the    disease have been studied in experimental animal model. Migration of immune cells to the central nervous system (CNS) is a predominant feature of MS. CD44 molecule has been reported to be involved in many  important biological processes including contribution in severing inflammation in experimental autoimmune encephalomyelitis (EAE). Matrix metalloprotease-9 (MMP-9) interaction with CD44 has been well known to be involved in cellular adhesion, transmigration and inflammation. In this study, we were interested to examine the role of phagocytic cells expressing MMP-9 in resolving EAE. Materials and Methods: C57BL/6 WT and CD44 KO mice were used as EAE animal model. The level of phagocytic cells expressing MMP-9 in the  secondary lymphoid organs were assessed in EAE induced WT as well as CD44 KO animals. Results: EAE severity was found in CD44 KO group compared to WT. Level of CD11b cells (marker of phagocytic cell) in the peritoneal cells expressing MMP-9 was higher in WT compared to CD44 KO. CD11b stained area found to be greater in WT lymph node compared to CD44 KO. Conclusions: This observation suggests the role of CD44 molecule in modulating the immune scenario which is related to disease severity. This study also opens avenues for the specific inflammatory roles of different immune cells in MS.Keywords: multiple sclerosis; EAE; CD44; MMP-9; CD11b; CNS. 

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.

scholarly journals Intermittent blockade of OGFr and treatment of autoimmune disorders

2018 ◽  
Vol 243 (17-18) ◽  
pp. 1323-1330 ◽  
Author(s):  
Ian S Zagon ◽  
Patricia J McLaughlin
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Growth Factor ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Disorders ◽  
Cell Replication ◽  
Autoimmune Encephalomyelitis ◽  
Opioid Growth Factor ◽  
Experimental Autoimmune

The opioid growth factor (OGF)–OGF receptor (OGFr) axis is present in normal and abnormal cells and tissues, and functions to maintain homeostatic cell replication. OGF is an inhibitory growth factor that upregulates p16 and/or p21 cyclin-dependent inhibitory kinases to slow cell replication. Blockade of this regulatory pathway can be intermittent or complete with the end result being depressed or accelerated, respectively, cell proliferation and growth. Intermittent blockade of the OGF–OGFr pathway with lose doses of naltrexone (LDN), a general opioid receptor antagonist, has been studied clinically in a number of autoimmune diseases, including fibromyalgia, Crohn’s, and multiple sclerosis (MS). Serum enkephalin levels were decreased in patients with MS relative to subjects with other neurological disorders. The intermittent blockade of OGFr by LDN results in a biofeedback mechanism that upregulates serum enkephalin levels. Clinical studies have reported that LDN is beneficial in enhancing quality of life, reducing fatigue, and increasing motor activity in humans with fibromyalgia, Crohn’s, or MS. LDN treatment is well tolerated even after several years of therapy. Preclinical investigations using experimental autoimmune encephalomyelitis (EAE), an animal model of MS mediated by T and B lymphocyte activation, demonstrate that immunization alone resulted in reduced enkephalin (i.e. OGF) levels. Therapy with LDN restored serum enkephalin levels in EAE mice resulting in improved EAE behavioral scores and diminished CNS pathology. This mini-review summarizes both preclinical and clinical data and focuses on the role of serum enkephalins resulting from intermittent blockade of OGFr by LDN in autoimmune disorders. Impact statement This mini-review presents information on the intermittent blockade of the opioid growth factor (OGF)–OGF receptor (OGFr) axis by low-dose naltrexone (LDN), and the role of enkephalin (i.e. OGF) in autoimmune disorders, specifically multiple sclerosis, Crohn’s, and fibromyalgia. Clinical reports on subjects taking LDN have documented reduced fatigue, few side-effects, and improved overall health. Preclinical studies on mice with experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, revealed that immunization for EAE reduces serum OGF. Intermittent OGFr blockade with LDN restores serum enkephalin levels that correlate with reduced behavioral and pathological signs of EAE; LDN also increases enkephalin levels in naïve mice. The interplay between LDN, and the onset and treatment of autoimmune diseases, chronic pain, and other addictive behaviors requires further investigation, but highlights a central role for enkephalins and intermittent blockade of the OGF–OGFr pathway in pathogenesis and treatment of these disorders.

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.

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 Immune-Modulatory Role of Apolipoprotein E with Emphasis on Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Hong-Liang Zhang ◽  
Jiang Wu ◽  
Jie Zhu
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Apolipoprotein E ◽  
T Cell Proliferation ◽  
Special Focus ◽  
Autoimmune Encephalomyelitis ◽  
Multiple Functions ◽  
Lipid Antigen ◽  
Experimental Autoimmune

Apolipoprotein E (apoE) is a 34.2 kDa glycoprotein characterized by its wide tissue distribution and multiple functions. The nonlipid-related properties of apoE include modulating inflammation and oxidation, suppressing T cell proliferation, regulating macrophage functions, and facilitating lipid antigen presentation by CD1 molecules to natural killer T (NKT) cells, and so forth. Increasing studies have revealed that APOEεallele might be associated with multiple sclerosis (MS), although evidence is still not sufficient enough. In this review, we summarized the current progress of the immunomodulatory functions of apoE, with special focus on the association of APOEεallele with the clinical features of MS and of its animal model experimental autoimmune encephalomyelitis (EAE).

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