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J Immunol. 2018 Feb 1;200(3):966-973. doi: 10.4049/jimmunol.1701484. Epub 2017 Dec 29.

GM-CSF Promotes Chronic Disability in Experimental Autoimmune Encephalomyelitis by Altering the Composition of Central Nervous System-Infiltrating Cells, but Is Dispensable for Disease Induction.

Duncker PC1,2,3, Stoolman JS1,2,3, Huber AK1,2, Segal BM4,2,3,5.

Author information

1
Holtom-Garrett Program in Neuroimmunology, Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48109.
2
Multiple Sclerosis Center, Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48109.
3
Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI 48109; and.
4
Holtom-Garrett Program in Neuroimmunology, Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48109; bmsegal@med.umich.edu.
5
Neuroscience Program, University of Michigan School of Medicine, Ann Arbor, MI 48109.

Abstract

GM-CSF has been portrayed as a critical cytokine in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and, ostensibly, in multiple sclerosis. C57BL/6 mice deficient in GM-CSF are resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 The mechanism of action of GM-CSF in EAE is poorly understood. In this study, we show that GM-CSF augments the accumulation of MOG35-55-specific T cells in the skin draining lymph nodes of primed mice, but it is not required for the development of encephalitogenic T cells. Abrogation of GM-CSF receptor signaling in adoptive transfer recipients of MOG35-55-specific T cells did not alter the incidence of EAE or the trajectory of its initial clinical course, but it limited the extent of chronic CNS tissue damage and neurologic disability. The attenuated clinical course was associated with a relative dearth of MOG35-55-specific T cells, myeloid dendritic cells, and neutrophils, as well as an abundance of B cells, within CNS infiltrates. Our data indicate that GM-CSF drives chronic tissue damage and disability in EAE via pleiotropic pathways, but it is dispensable during early lesion formation and the onset of neurologic deficits.

PMID:
29288202
PMCID:
PMC5780231
[Available on 2019-02-01]
DOI:
10.4049/jimmunol.1701484
[Indexed for MEDLINE]

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