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Twin study identifies early immunological and metabolic dysregulation of CD8+ T cells in multiple sclerosis

Multiple sclerosis (MS) is an inflammatory neurological disease of the central nervous system with a subclinical phase preceding frank neuroinflammation. CD8+ T cells are abundant within MS lesions, but their potential role in disease pathology remains unclear. Using high-throughput single-cell RNA...

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Main Authors: Kavaka, Vladyslav (Author) , Mutschler, Luisa (Author) , Rosa del Val, Clara de la (Author) , Eglseer, Klara (Author) , Gómez Martínez, Ana M. (Author) , Flierl-Hecht, Andrea (Author) , Ertl-Wagner, Birgit (Author) , Keeser, Daniel (Author) , Mortazavi, Martin (Author) , Seelos, Klaus (Author) , Zimmermann, Hanna (Author) , Haas, Jürgen (Author) , Wildemann, Brigitte (Author) , Kümpfel, Tania (Author) , Dornmair, Klaus (Author) , Korn, Thomas (Author) , Hohlfeld, Reinhard (Author) , Kerschensteiner, Martin (Author) , Gerdes, Lisa Ann (Author) , Beltrán, Eduardo (Author)
Format: Article (Journal)
Language:English
Published: 2024
In: Science immunology
Year: 2024, Volume: 9, Issue: 99, Pages: ?
ISSN:2470-9468
DOI:10.1126/sciimmunol.adj8094
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/sciimmunol.adj8094
Verlag, lizenzpflichtig, Volltext: https://www.science.org/doi/10.1126/sciimmunol.adj8094
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Author Notes:Vladyslav Kavaka, Luisa Mutschler, Clara de la Rosa del Val, Klara Eglseer, Ana M. Gómez Martínez, Andrea Flierl-Hecht, Birgit Ertl-Wagner, Daniel Keeser, Martin Mortazavi, Klaus Seelos, Hanna Zimmermann, Jürgen Haas, Brigitte Wildemann, Tania Kümpfel, Klaus Dornmair, Thomas Korn, Reinhard Hohlfeld, Martin Kerschensteiner, Lisa Ann Gerdes, Eduardo Beltrán
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Summary:Multiple sclerosis (MS) is an inflammatory neurological disease of the central nervous system with a subclinical phase preceding frank neuroinflammation. CD8+ T cells are abundant within MS lesions, but their potential role in disease pathology remains unclear. Using high-throughput single-cell RNA sequencing and single-cell T cell receptor analysis, we compared CD8+ T cell clones from the blood and cerebrospinal fluid (CSF) of monozygotic twin pairs in which the cotwin had either no or subclinical neuroinflammation (SCNI). We identified peripheral MS-associated immunological and metabolic alterations indicative of an enhanced migratory, proinflammatory, and activated CD8+ T cell phenotype, which was also evident in cotwins with SCNI and in an independent validation cohort of people with MS. Together, our in-depth single-cell analysis indicates a disease-driving proinflammatory role of infiltrating CD8+ T cells and identifies potential immunological and metabolic therapeutic targets in both prodromal and definitive stages of the disease.
Item Description:Das Pluszeichen im Titel ist hochgestellt
Online veröffentlicht: 27. September 2024
Gesehen am 26.03.2025
Physical Description:Online Resource
ISSN:2470-9468
DOI:10.1126/sciimmunol.adj8094

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