Abstract
Multiple sclerosis (MS) is an immune-mediated disease that predominantly impacts the central nervous system (CNS). Animal models have been used to elucidate the underpinnings of MS pathology. One of the most well-studied models of MS is experimental autoimmune encephalomyelitis (EAE). This model was utilized to demonstrate that the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical and non-redundant role in mediating EAE pathology, making it an ideal therapeutic target. In this review, we will first explore the role that GM-CSF plays in maintaining homeostasis. This is important to consider, because any therapeutics that target GM-CSF could potentially alter these regulatory processes. We will then focus on current findings related to the function of GM-CSF signaling in EAE pathology, including the cell types that produce and respond to GM-CSF and the role of GM-CSF in both acute and chronic EAE. We will then assess the role of GM-CSF in alternative models of MS and comment on how this informs the understanding of GM-CSF signaling in the various aspects of MS immunopathology. Finally, we will examine what is currently known about GM-CSF signaling in MS, and how this has promoted clinical trials that directly target GM-CSF.
Highlights
Multiple sclerosis (MS) is a chronic immune-mediated disease that impacts approximately 2.3 million people world-wide [1]
We will assess the role of granulocyte-macrophage colony-stimulating factor (GM-cerebral spinal fluid (CSF)) in alternative models of MS and comment on how this informs the understanding of GM-CSF signaling in the various aspects of MS immunopathology
Given that alveolar macrophages play a major role in facilitating the clearance of surfactant from the alveolar space, GM-CSF-deficient mice develop a condition known as pulmonary alveolar proteinosis (PAP), which is characterized by the accumulation of surfactant in the alveolar space [23,24]
Summary
Multiple sclerosis (MS) is a chronic immune-mediated disease that impacts approximately 2.3 million people world-wide [1]. Cells 2020, 9, 611 with differing clinical manifestations, it is important to distinguish between these subtypes This is because the current disease-modifying agents that are used to treat MS are efficacious at treating neuroinflammation and abrogating some of the tissue damage and demyelination associated with the active phase of the disease, when patients exhibit overt clinical symptoms [6,7,8]. This model has been used to identify novel therapeutic targets by ascertaining those mediators that are critical for potentiating neuroinflammation One such mediator that has gained attention for its role in promoting EAE-associated inflammation is the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). We will explore the studies that have directly ascertained the function of GM-CSF in MS, and what implications these findings have for developing novel therapies that target GM-CSF and its downstream mediators
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