GM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis.
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Galli E
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
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Hartmann FJ
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
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Schreiner B
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
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Ingelfinger F
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
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Arvaniti E
Institute for Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
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Diebold M
Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
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Mrdjen D
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
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van der Meer F
Institut für Neuropathologie, Klinik für Neurologie, Universitätsmedizin Göttingen, Gottingen, Germany.
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Krieg C
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
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Nimer FA
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
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Sanderson N
Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
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Stadelmann C
Institut für Neuropathologie, Klinik für Neurologie, Universitätsmedizin Göttingen, Gottingen, Germany.
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Khademi M
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
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Piehl F
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
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Claassen M
Institute for Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
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Derfuss T
Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
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Olsson T
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
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Becher B
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland. becher@immunology.uzh.ch.
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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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green
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https://sonar.ch/global/documents/286587
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