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
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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