scholarly journals The Ifng Gene Is Essential for Vdr Gene Expression and Vitamin D3-Mediated Reduction of the Pathogenic T Cell Burden in the Central Nervous System in Experimental Autoimmune Encephalomyelitis, a Multiple Sclerosis Model

2012 ◽  
Vol 189 (6) ◽  
pp. 3188-3197 ◽  
Author(s):  
Justin A. Spanier ◽  
Faye E. Nashold ◽  
Julie K. Olson ◽  
Colleen E. Hayes
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Autoimmune Encephalomyelitis ◽  
Vdr Gene ◽  
Ifng Gene ◽  
The Central Nervous System ◽  
Mediated Reduction ◽  
Multiple Sclerosis Model ◽  
Experimental Autoimmune

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 TGF-β in Mice Ameliorates Experimental Autoimmune Encephalomyelitis in Regulating NK Cell Activity

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1155-1160 ◽  
Author(s):  
J. Xu ◽  
Y. Wang ◽  
H. Jiang ◽  
M. Sun ◽  
J. Gao ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Nk Cells ◽  
Nk Cell ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

Multiple sclerosis is a disease characterized by inflammation and demyelination located in the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is the most common animal model for multiple sclerosis (MS). Although the roles of T cells in MS/EAE have been well investigated, little is known about the functions of other immune cells in the neuroinflammation model. Here we found that an essential cytokine transforming growth factor β (TGF-β) which could mediate the differentiation of Th17/regulatory T cells was implicated in the natural killer (NK) cells’ activity in EAE. In EAE mice, TGF-β expression was first increased at the onset and then decreased at the peak, but the expressions of TGF-β receptors and downstream molecules were not affected in EAE. When we immunized the mice with MOG antigen, it was revealed that TGF-β treatment reduced susceptibility to EAE with a lower clinical score than the control mice without TGF-β. Consistently, inflammatory cytokine production was reduced in the TGF-β treated group, especially with downregulated pathogenic interleukin-17 in the central nervous system tissue. Furthermore, TGF-β could increase the transcription level of NK cell marker NCR1 both in the spleen and in the CNS without changing other T cell markers. Meanwhile TGF-β promoted the proliferation of NK cell proliferation. Taken together, our data demonstrated that TGF-β could confer protection against EAE model in mice through NK cells, which would be useful for the clinical therapy of MS.

scholarly journals Caspase-11 Mediates Oligodendrocyte Cell Death and Pathogenesis of Autoimmune-Mediated Demyelination

2001 ◽  
Vol 193 (1) ◽  
pp. 111-122 ◽  
Author(s):  
Shin Hisahara ◽  
Junying Yuan ◽  
Takashi Momoi ◽  
Hideyuki Okano ◽  
Masayuki Miura
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Cell Death ◽  
Caspase 3 ◽  
Inflammatory Diseases ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Deficient Mice ◽  
Experimental Autoimmune

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory diseases of the central nervous system (CNS) characterized by localized areas of demyelination. The mechanisms underlying oligodendrocyte (OLG) injury in MS and EAE remain unknown. Here we show that caspase-11 plays crucial roles in OLG death and pathogenesis in EAE. Caspase-11 and activated caspase-3 were both expressed in OLGs in spinal cord EAE lesions. OLGs from caspase-11–deficient mice were highly resistant to the cell death induced by cytotoxic cytokines. EAE susceptibility and cytokine concentrations in the CNS were significantly reduced in caspase-11–deficient mice. Our findings suggest that OLG death is mediated by a pathway that involves caspases-11 and -3 and leads to the demyelination observed in EAE.

scholarly journals Regulation of Immune Cell Infiltration into the CNS by Regional Neural Inputs Explained by the Gate Theory

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yasunobu Arima ◽  
Daisuke Kamimura ◽  
Lavannya Sabharwal ◽  
Moe Yamada ◽  
Hidenori Bando ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cancer Metastasis ◽  
Immune Cell ◽  
Immune Cell Infiltration ◽  
Virus Infections ◽  
Autoimmune Encephalomyelitis ◽  
Mechanical Disruption ◽  
The Central Nervous System ◽  
Experimental Autoimmune

The central nervous system (CNS) is an immune-privileged environment protected by the blood-brain barrier (BBB), which consists of specific endothelial cells that are brought together by tight junctions and tight liner sheets formed by pericytes and astrocytic end-feet. Despite the BBB, various immune and tumor cells can infiltrate the CNS parenchyma, as seen in several autoimmune diseases like multiple sclerosis (MS), cancer metastasis, and virus infections. Aside from a mechanical disruption of the BBB like trauma, how and where these cells enter and accumulate in the CNS from the blood is a matter of debate. Recently, using experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we found a “gateway” at the fifth lumber cord where pathogenic autoreactive CD4+ T cells can cross the BBB. Interestingly, this gateway is regulated by regional neural stimulations that can be mechanistically explained by the gate theory. In this review, we also discuss this theory and its potential for treating human diseases.

scholarly journals Analysis of the Runx3 expression during experiemental autoimmune encephalomyelitis

2018 ◽  
Author(s):  
Beatriz Souza Lopes ◽  
Alessandro dos Santos Farias ◽  
Ana Maria Marques
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Demyelinating Disease ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Effector Activity ◽  
Runx3 Gene ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS), which is attributed to a self-sustaining autoimmune mechanism. The majority of the knowledge regarding MS autoagressive mechanisms is resultant of studies performed in its experimental model (mice) the experimental autoimmune encephalomyelitis (EAE).Although, the literature reports that the EAE is mediated by proinflammatory CD4+ T cells , isn’t completely clear how these cells (known as helper cells) would be able of initiate the disease when adoptively transferred to healthy animals.We believe that the Runx3 gene presents a central role in the progression and regulation of the effector activity in CD4+ encephalitogenic lymphocytes.

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