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Nat Med. 2019 Aug;25(8):1290-1300. doi: 10.1038/s41591-019-0521-4. Epub 2019 Jul 22.

GM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis.

Author information

1
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
2
Department of Dermatology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
3
Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
4
Institute for Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
5
Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
6
Institut für Neuropathologie, Klinik für Neurologie, Universitätsmedizin Göttingen, Gottingen, Germany.
7
Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
8
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
9
Department of Pathology, School of Medicine, Stanford University, Palo Alto, CA, USA.
10
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland. becher@immunology.uzh.ch.

Abstract

Cytokine dysregulation is a central driver of chronic inflammatory diseases such as multiple sclerosis (MS). Here, we sought to determine the characteristic cellular and cytokine polarization profile in patients with relapsing-remitting multiple sclerosis (RRMS) by high-dimensional single-cell mass cytometry (CyTOF). Using a combination of neural network-based representation learning algorithms, we identified an expanded T helper cell subset in patients with MS, characterized by the expression of granulocyte-macrophage colony-stimulating factor and the C-X-C chemokine receptor type 4. This cellular signature, which includes expression of very late antigen 4 in peripheral blood, was also enriched in the central nervous system of patients with relapsing-remitting multiple sclerosis. In independent validation cohorts, we confirmed that this cell population is increased in patients with MS compared with other inflammatory and non-inflammatory conditions. Lastly, we also found the population to be reduced under effective disease-modifying therapy, suggesting that the identified T cell profile represents a specific therapeutic target in MS.

PMID:
31332391
PMCID:
PMC6689469
[Available on 2020-01-22]
DOI:
10.1038/s41591-019-0521-4

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