Format

Send to

Choose Destination
J Exp Med. 2015 Jan 12;212(1):23-35. doi: 10.1084/jem.20141015. Epub 2015 Jan 5.

Neutrophil-related factors as biomarkers in EAE and MS.

Author information

1
Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109.
2
Department of Neuroimmunology, Max Planck Institute for Neurobiology, 82152 Martinsried, Germany.
3
Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109 Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109 Neurology Service, VA Ann Arbor Healthcare System, Ann Arbor, MI 48105 bmsegal@umich.edu.

Abstract

A major function of T helper (Th) 17 cells is to induce the production of factors that activate and mobilize neutrophils. Although Th17 cells have been implicated in the pathogenesis of multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE), little attention has been focused on the role of granulocytes in those disorders. We show that neutrophils, as well as monocytes, expand in the bone marrow and accumulate in the circulation before the clinical onset of EAE, in response to systemic up-regulation of granulocyte colony-stimulating factor (G-CSF) and the ELR(+) CXC chemokine CXCL1. Neutrophils comprised a relatively high percentage of leukocytes infiltrating the central nervous system (CNS) early in disease development. G-CSF receptor deficiency and CXCL1 blockade suppressed myeloid cell accumulation in the blood and ameliorated the clinical course of mice that were injected with myelin-reactive Th17 cells. In relapsing MS patients, plasma levels of CXCL5, another ELR(+) CXC chemokine, were elevated during acute lesion formation. Systemic expression of CXCL1, CXCL5, and neutrophil elastase correlated with measures of MS lesion burden and clinical disability. Based on these results, we advocate that neutrophil-related molecules be further investigated as novel biomarkers and therapeutic targets in MS.

PMID:
25559893
PMCID:
PMC4291533
DOI:
10.1084/jem.20141015
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center