scholarly journals Reduction in CD11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination

2021 ◽  
pp. 105556
Author(s):  
Florian Mayrhofer ◽  
Zhanna Dariychuk ◽  
Anthony Zhen ◽  
Daniel J. Daugherty ◽  
Peter Bannerman ◽  
...  
Keyword(s):  
Clinical Progression ◽  
Autoimmune Demyelination ◽  
Experimental Autoimmune

scholarly journals Differential roles of microglia and monocytes in the inflamed central nervous system

2014 ◽  
Vol 211 (8) ◽  
pp. 1533-1549 ◽  
Author(s):  
Ryo Yamasaki ◽  
Haiyan Lu ◽  
Oleg Butovsky ◽  
Nobuhiko Ohno ◽  
Anna M. Rietsch ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Expression Profiles ◽  
Disease Onset ◽  
Gene Expression Profiles ◽  
Autoimmune Encephalomyelitis ◽  
Block Face ◽  
Human Disorder ◽  
Autoimmune Demyelination ◽  
New Strategies ◽  
Experimental Autoimmune

In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell–mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood. In the present study, we addressed the cellular basis of autoimmune demyelination by discriminating microglial versus monocyte origins of effector macrophages. Using serial block-face scanning electron microscopy (SBF-SEM), we show that monocyte-derived macrophages associate with nodes of Ranvier and initiate demyelination, whereas microglia appear to clear debris. Gene expression profiles confirm that monocyte-derived macrophages are highly phagocytic and inflammatory, whereas those arising from microglia demonstrate an unexpected signature of globally suppressed cellular metabolism at disease onset. Distinguishing tissue-resident macrophages from infiltrating monocytes will point toward new strategies to treat disease and promote repair in diverse inflammatory pathologies in varied organs.

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 Reduction in CD11c+ microglia promotes clinical progression in autoimmune demyelination

2018 ◽  
Author(s):  
Florian Mayrhofer ◽  
Zhanna Dariychuk ◽  
Anthony Zhen ◽  
Daniel J. Daugherty ◽  
Peter Bannerman ◽  
...  
Keyword(s):  
Immune Cell ◽  
Severe Disease ◽  
Underlying Disease ◽  
Perivascular Spaces ◽  
Clinical Progression ◽  
Autoimmune Encephalomyelitis ◽  
Progressive Decline ◽  
Demyelinating Disorder ◽  
Relapsing Remitting ◽  
Autoimmune Demyelination

AbstractMultiple sclerosis (MS) is a chronic autoimmune demyelinating disorder. Most people with MS show a relapsing-remitting disease course that over time transitions into progressive decline of neurologic function. The mechanisms underlying disease progression in MS remain poorly understood. Here we demonstrate that reduction in CD11c+ microglia promotes dispersed coalescent parenchymal infiltration and clinical progression in chronic mild experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We found sex-dependent differences in EAE progression mediated by p38α signaling, a key regulator of inflammation. CD11c promoter-driven knockout of p38α (KO) reduced CD11c+ microglia proliferation in female mice and promoted CNS infiltration and transition of chronic mild to severe disease. In protected KO males, immune cells were trapped within perivascular spaces and prevented from crossing the glia limitans closely surrounded by dendritic cell-like CD11c+ microglia. Together, our study provides the first evidence that in chronic mild EAE, CD11c+ microglia interact with astrocytes to control CNS immune cell parenchymal infiltration.

scholarly journals Beneficial or Harmful Role of Macrophages in Guillain-Barré Syndrome and Experimental Autoimmune Neuritis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Donghui Shen ◽  
Fengna Chu ◽  
Yue Lang ◽  
Yunlong Geng ◽  
Xiangyu Zheng ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Critical Role ◽  
Decisive Role ◽  
Guillain Barre Syndrome ◽  
Experimental Autoimmune Neuritis ◽  
Guillain Barré Syndrome ◽  
Anti Inflammatory ◽  
Autoimmune Demyelination ◽  
Guillain Barré ◽  
Experimental Autoimmune

Guillain-Barré syndrome (GBS), an immune-mediated demyelinating peripheral neuropathy, is characterized by acute weakness of the extremities and areflexia or hyporeflexia. Experimental autoimmune neuritis (EAN) is a common animal model for GBS, which represents a CD4+ T cell-mediated inflammatory autoimmune demyelination of the peripheral nervous system (PNS), and is used to investigate the pathogenic mechanism of GBS. It has been found that macrophages play a critical role in the pathogenesis of both GBS and EAN. Macrophages have been primarily classified into two major phenotypes: proinflammatory macrophages (M1) and anti-inflammatory macrophages (M2). The two different macrophage subsets M1 and M2 may play a decisive role in initiation and development of GBS and EAN. However, recently, it has been indicated that the roles of macrophages in immune regulation and autoimmune diseases are more complex than those suggested by a simple M1-M2 dichotomy. Macrophages might exert either inflammatory or anti-inflammatory effect by secreting pro- or anti-inflammatory cytokines, and either inducing the activation of T cells to mediate immune response, resulting in inflammation and demyelination in the PNS, or promoting disease recovery. In this review, we summarize the dual roles of macrophages in GBS and EAN and explore the mechanism of macrophage polarization to provide a potential therapeutic approach for GBS in the future.

Synapsin I deletion reduces neuronal damage and ameliorates clinical progression of experimental autoimmune encephalomyelitis

2018 ◽  
Vol 68 ◽  
pp. 197-210
Author(s):  
Fabrizia C. Guarnieri ◽  
Serena Bellani ◽  
Latefa Yekhlef ◽  
Andrea Bergamaschi ◽  
Annamaria Finardi ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Neuronal Damage ◽  
Synapsin I ◽  
Clinical Progression ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Neuronal NF-κB ablation does not influence neuro-axonal degeneration in experimental autoimmune demyelination

2012 ◽  
Vol 246 (1-2) ◽  
pp. 38-42 ◽  
Author(s):  
De-Hyung Lee ◽  
Katharina Kubera ◽  
Bastian Rosenthal ◽  
Barbara Kaltschmidt ◽  
Christian Kaltschmidt ◽  
...  
Keyword(s):  
Axonal Degeneration ◽  
Autoimmune Demyelination ◽  
Experimental Autoimmune

scholarly journals A Clonal NG2-Glia Cell Response in a Mouse Model of Multiple Sclerosis

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1279 ◽  
Author(s):  
Sonsoles Barriola ◽  
Fernando Pérez-Cerdá ◽  
Carlos Matute ◽  
Ana Bribián ◽  
Laura López-Mascaraque
Keyword(s):  
Multiple Sclerosis ◽  
Brain Damage ◽  
Tissue Repair ◽  
Phenotypic Diversity ◽  
Demyelinating Diseases ◽  
Autoimmune Encephalomyelitis ◽  
Oligodendrocyte Precursor ◽  
Autoimmune Demyelination ◽  
The Brain ◽  
Experimental Autoimmune

NG2-glia, also known as oligodendrocyte precursor cells (OPCs), have the potential to generate new mature oligodendrocytes and thus, to contribute to tissue repair in demyelinating diseases like multiple sclerosis (MS). Once activated in response to brain damage, NG2-glial cells proliferate, and they acquire a reactive phenotype and a heterogeneous appearance. Here, we set out to investigate the distribution and phenotypic diversity of NG2-glia relative to their ontogenic origin, and whether there is a clonal NG2-glial response to lesion in an experimental autoimmune encephalomyelitis (EAE) murine model of MS. As such, we performed in utero electroporation of the genomic lineage tracer, StarTrack, to follow the fate of NG2-glia derived from single progenitors and to evaluate their response to brain damage after EAE induction. We then analyzed the dispersion of the NG2-glia derived clonally from single pallial progenitors in the brain of EAE mice. In addition, we examined several morphological parameters to assess the degree of NG2-glia reactivity in clonally-related cells. Our results reveal the heterogeneity of these progenitors and their cell progeny in a scenario of autoimmune demyelination, revealing the ontogenic phenomena at play in these processes.

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