| First Author | Pierson ER | Year | 2017 |
| Journal | JCI Insight | Volume | 2 |
| Issue | 7 | Pages | e92362 |
| PubMed ID | 28405624 | Mgi Jnum | J:288050 |
| Mgi Id | MGI:6407549 | Doi | 10.1172/jci.insight.92362 |
| Citation | Pierson ER, et al. (2017) GM-CSF is not essential for experimental autoimmune encephalomyelitis but promotes brain-targeted disease. JCI Insight 2(7):e92362 |
| abstractText | 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-gamma 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-gamma 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. |
