GM-CSF is not essential for experimental autoimmune encephalomyelitis but promotes brain-targeted disease
Emily R. Pierson, Joan M. Goverman
Emily R. Pierson, Joan M. Goverman
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Research Article

GM-CSF is not essential for experimental autoimmune encephalomyelitis but promotes brain-targeted disease

Abstract

Experimental autoimmune encephalomyelitis (EAE) has been used as an animal model of multiple sclerosis to identify pathogenic cytokines that could be therapeutic targets. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is the only cytokine reported to be essential for EAE. We investigated the role of GM-CSF in EAE in C3HeB/FeJ mice that uniquely exhibit extensive brain and spinal cord inflammation. Unexpectedly, GM-CSF–deficient C3HeB/FeJ mice were fully susceptible to EAE because IL-17 activity compensated for the loss of GM-CSF during induction of spinal cord–targeted disease. In contrast, both GM-CSF and IL-17 were needed to fully overcome the inhibitory influence of IFN-γ on the induction of inflammation in the brain. Both GM-CSF and IL-17 independently promoted neutrophil accumulation in the brain, which was essential for brain-targeted disease. These results identify a GM-CSF/IL-17/IFN-γ axis that regulates inflammation in the central nervous system and suggest that a combination of cytokine-neutralizing therapies may be needed to dampen central nervous system autoimmunity.

Authors

Emily R. Pierson, Joan M. Goverman

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Figure 1

GM-CSF is not required for EAE in C3HeB/FeJ mice.

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GM-CSF is not required for EAE in C3HeB/FeJ mice. Mean clinical scores f...
Mean clinical scores for mice that developed EAE following transfer of IL-23–conditioned T cells from MOG-immunized WT or Csf2–/– donors into WT or Csf2–/– recipients. Data are pooled from 3 experiments in which WT T cells were transferred into a total of 12 WT recipients or a total of 11 Csf2–/– recipients, and Csf2–/– T cells were transferred into a total of 12 WT recipients or a total of 13 Csf2–/– recipients. Mean clinical scores (± SEM) were determined using a single numerical scoring system that includes both atypical and classic signs as described in Methods. EAE, experimental autoimmune encephalomyelitis; GM-CSF, granulocyte-macrophage colony-stimulating factor; MOG, myelin oligodendrocyte glycoprotein.