GM-CSF in Autoimmune Inflammation of the Central Nervous System

El-Behi, Mohamed; Ćirić, Bogoljub; Rostami, Abdolmohamad

doi:10.1007/978-1-4614-7953-6_7

Cited by 2 publications

(1 citation statement)

References 128 publications

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“…These cells may lose their BDNF responsiveness as they mature. Th17 cells have recently been identified as playing a critical role in the MS disease process (El-Behi et al, 2010). However, there have been no studies investigating the role of BDNF in the regulation of Th17 cells.…”

Section: Discussionmentioning

confidence: 99%

Spinal Cord Brain Derived Neurotrophic Factor (BDNF) Responsive Cells in an Experimental Autoimmune Encephalomyelitis (EAE) Model of Multiple Sclerosis (MS): Implications in Myelin Repair

Zhu¹,

Acosta²,

MacNeil³

et al. 2014

IMMU

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Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that destroys central nervous system (CNS) myelin. Although, the exact pathophysiology of MS is unknown, it is associated with CNS infiltration of T-cells and monocytes, which subsequently activate phagocytic cells that directly damage myelin. Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor (TrkB), have recognized roles in myelin structure formation, maintenance, and repair. We used an experimental autoimmune encephalomyelitis (EAE) model of MS to determine changes in TrkB expression that may contribute to neurological recovery and myelin repair following an early inflammatory immune-mediated attack on CNS myelin. Spinal cord (SC) TrkB gene and protein expression were analyzed at various time intervals post-EAE induction. Analysis of gene and protein expression was conducted in animals with EAE relative to active controls (AC) and naïve controls (NC). We showed significant increases in TrkB protein in the SC of EAE rats 12 days post-induction relative to controls. This elevated TrkB expression correlated with the onset of neurological recovery days 12 to 15 post-EAE induction. Furthermore, immunohistochemistry (IHC) analysis revealed up-regulated expression of TrkB in several SC cell types including a specific subset of BDNF responsive neuronal cells. Finally, transmission electron microscopy (TEM) showed the ultrastructural integrity of myelin is already compromised during the early,

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Section: Discussionmentioning

confidence: 99%

Spinal Cord Brain Derived Neurotrophic Factor (BDNF) Responsive Cells in an Experimental Autoimmune Encephalomyelitis (EAE) Model of Multiple Sclerosis (MS): Implications in Myelin Repair

Zhu¹,

Acosta²,

MacNeil³

et al. 2014

IMMU

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The role of granulocyte‐macrophage colony‐stimulating factor in the pathogenesis of neuromyelitis optica: A white or black knight?

Masuda

Uzawa

Mori

et al. 2015

Clinical & Exp Neuroim

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Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) not only induces the differentiation of hematopoietic cells into granulocytes and macrophages but also exerts immunomodulatory functions. GM‐CSF promotes experimental autoimmune encephalomyelitis, multiple sclerosis, and rheumatoid arthritis. Conversely, GM‐CSF ameliorates some type 2 helper T cell‐dominant diseases, including experimental autoimmune myasthenia gravis, experimental autoimmune thyroiditis, Crohn's disease, type 1 diabetes mellitus, autoimmune neutropenia, and juvenile systemic lupus erythematosus. However, the contribution of GM‐CSF to the pathogenesis of neuromyelitis optica (NMO) has not been studied. In this article, we review GM‐CSF roles in the central nervous system and report evidence that GM‐CSF may positively affect the pathogenesis of NMO. We have previously reported (i) that patients with NMO expressing antinuclear antibodies (ANA‐positive) have less severe disease activity and a better prognosis than ANA‐negative patients and (ii) an analysis of the cytokine/chemokine profiles of 24 patients with NMO. We investigated associations between cytokine expression, ANA‐positivity, and disease severity. Among the 24 patients, the six who were ANA positive had significantly elevated serum GM‐CSF concentrations than the ANA‐negative patients (medians: 7.0 vs 0.27 pg/mL, respectively; P = 0.001) and higher cerebrospinal fluid GM‐CSF concentrations (medians: 53.7 vs 47.0 pg/mL, respectively; P = 0.068). Although no other cytokine/chemokine profiles were different based on ANA status, cerebrospinal fluid GM‐CSF concentrations at relapse were negatively correlated with Kurtzke Expanded Disability Status Scale scores (R2 = 0.26, P = 0.009). Therefore, GM‐CSF may play a protective role in the pathogenesis of NMO.

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GM-CSF in Autoimmune Inflammation of the Central Nervous System

Cited by 2 publications

References 128 publications

Spinal Cord Brain Derived Neurotrophic Factor (BDNF) Responsive Cells in an Experimental Autoimmune Encephalomyelitis (EAE) Model of Multiple Sclerosis (MS): Implications in Myelin Repair

Spinal Cord Brain Derived Neurotrophic Factor (BDNF) Responsive Cells in an Experimental Autoimmune Encephalomyelitis (EAE) Model of Multiple Sclerosis (MS): Implications in Myelin Repair

The role of granulocyte‐macrophage colony‐stimulating factor in the pathogenesis of neuromyelitis optica: A white or black knight?

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