GM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis
Autor: | Manfred Claassen, Nicholas S. R. Sanderson, Eirini Arvaniti, Felix J. Hartmann, Martin Diebold, Burkhard Becher, Mohsen Khademi, Fredrik Piehl, Dunja Mrdjen, Tobias Derfuss, Edoardo Galli, Tomas Olsson, Christine Stadelmann, Faiez Al Nimer, Carsten Krieg, Bettina Schreiner, Franziska van der Meer, Florian Ingelfinger |
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Přispěvatelé: | University of Zurich, Becher, Burkhard |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Receptors CXCR4 Multiple Sclerosis medicine.medical_treatment T cell Population 610 Medicine & health 10263 Institute of Experimental Immunology CXCR4 Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Chemokine receptor 0302 clinical medicine 1300 General Biochemistry Genetics and Molecular Biology Medicine Humans Mass cytometry education education.field_of_study business.industry Multiple sclerosis Granulocyte-Macrophage Colony-Stimulating Factor General Medicine T helper cell T-Lymphocytes Helper-Inducer medicine.disease 10040 Clinic for Neurology 030104 developmental biology medicine.anatomical_structure Cytokine 030220 oncology & carcinogenesis Immunology 570 Life sciences biology Cytokines business Immunologic Memory Algorithms Signal Transduction |
Zdroj: | Nature Medicine, 25 (8) Nature medicine |
ISSN: | 1546-170X |
Popis: | 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. |
Databáze: | OpenAIRE |
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