Journal article

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

  • Galli E Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Hartmann FJ Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Schreiner B Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Ingelfinger F Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Arvaniti E Institute for Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
  • Diebold M Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
  • Mrdjen D Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • van der Meer F Institut für Neuropathologie, Klinik für Neurologie, Universitätsmedizin Göttingen, Gottingen, Germany.
  • Krieg C Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Nimer FA Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Sanderson N Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
  • Stadelmann C Institut für Neuropathologie, Klinik für Neurologie, Universitätsmedizin Göttingen, Gottingen, Germany.
  • Khademi M Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Piehl F Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Claassen M Institute for Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
  • Derfuss T Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
  • Olsson T Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Becher B Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland. becher@immunology.uzh.ch.
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  • 2019-07-24
Published in:
  • Nature medicine. - 2019
English 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.
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  • English
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https://sonar.ch/global/documents/286587
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