scholarly journals The Th17–ELR+ CXC chemokine pathway is essential for the development of central nervous system autoimmune disease

2008 ◽  
Vol 205 (4) ◽  
pp. 811-823 ◽  
Author(s):  
Thaddeus Carlson ◽  
Mark Kroenke ◽  
Praveen Rao ◽  
Thomas E. Lane ◽  
Benjamin Segal
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Th17 Cells ◽  
Polymorphonuclear Leukocytes ◽  
Autoimmune Encephalomyelitis ◽  
Cxc Chemokine ◽  
The Central Nervous System ◽  
Autoimmune Demyelination ◽  
Clinical Deficits ◽  
Experimental Autoimmune

The ELR+ CXC chemokines CXCL1 and CXCL2 are up-regulated in the central nervous system (CNS) during multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, their functional significance and the pathways regulating their expression are largely unknown. We show that transfer of encephalitogenic CD4+ Th17 cells is sufficient to induce CXCL1 and CXCL2 transcription in the spinal cords of naive, syngeneic recipients. Blockade or genetic silencing of CXCR2, a major receptor for these chemokines in mice, abrogates blood–brain barrier (BBB) breakdown, CNS infiltration by leukocytes, and the development of clinical deficits during the presentation as well as relapses of EAE. Depletion of circulating polymorphonuclear leukocytes (PMN) had a similar therapeutic effect. Furthermore, injection of CXCR2+ PMN into CXCR2−/− mice was sufficient to restore susceptibility to EAE. Our findings reveal that a Th17–ELR+ CXC chemokine pathway is critical for granulocyte mobilization, BBB compromise, and the clinical manifestation of autoimmune demyelination in myelin peptide–sensitized mice, and suggest new therapeutic targets for diseases such as MS.

scholarly journals Study of the switch-over from the profile Th17 lymphocytes to Th1-like during the evolution of experimental autoimmune encephalomyelitis

2018 ◽  
Author(s):  
Bruna Bueno de Campos ◽  
Alessandro dos Santos Farias ◽  
Rani Cocenza ◽  
Fernando Pradella
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Cytotoxic Activity ◽  
Crucial Role ◽  
Th17 Cells ◽  
Autoimmune Encephalomyelitis ◽  
Th17 Lymphocytes ◽  
The Central Nervous System ◽  
Experimental Autoimmune

It has been demonstrated the cytotoxic activity of TCD4+ encaphalitogenic lymphocytes and it's crucial role in the development of Experimental Autoimmune Encephalomyelitis (EAE). Furthermore, our laboratory has seen a switch from Th17 profile to Th1-like during the evolution of EAE. Thus, these lymphocytes decreased IL-17A production while begin to produce IFNγ when infiltrate the central nervous system. Therefore, our goal was to verify the mechanisms that governs the convertion of Th17 cells into IFNγ-producing 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 Amino acid sequence of the encephalitogenic basic protein from human myelin

1971 ◽  
Vol 123 (1) ◽  
pp. 57-67 ◽  
Author(s):  
P. R. Carnegie
Keyword(s):  
Amino Acids ◽  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Basic Protein ◽  
Structure And Function ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
And Function ◽  
Experimental Autoimmune

Myelin from the central nervous system contains an unusual basic protein, which can induce experimental autoimmune encephalomyelitis. The basic protein from human brain was digested with trypsin and other enzymes and the sequence of the 170 amino acids was determined. The localization of the encephalitogenic determinants was described. Possible roles for the protein in the structure and function of myelin are discussed.

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