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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cytokines / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
  • Humans
  • Immunologic Memory
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / immunology*
  • Receptors, CXCR4 / biosynthesis*
  • T-Lymphocytes, Helper-Inducer / immunology*


  • CXCR4 protein, human
  • Cytokines
  • Receptors, CXCR4
  • Granulocyte-Macrophage Colony-Stimulating Factor