title: 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.forename: Emily R
authors.initials: ER
authors.lastname: Pierson
authors.forename: Joan M
authors.initials: JM
authors.lastname: Goverman
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D001921:Brain / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D020381:Interleukin-17; D016178:Granulocyte-Macrophage Colony-Stimulating Factor