ORCID: https://orcid.org/0009-0004-5837-3384; Mutschler, Luisa; Rosa del Val, Clara de la ORCID: https://orcid.org/0000-0002-1344-0844; Eglseer, Klara; Gómez Martínez, Ana M.; Flierl-Hecht, Andrea ORCID: https://orcid.org/0000-0002-2359-1128; Ertl-Wagner, Birgit B ORCID: https://orcid.org/0000-0002-7896-7049; Keeser, Daniel ORCID: https://orcid.org/0000-0002-0244-1024; Mortazavi, Martin ORCID: https://orcid.org/0000-0002-0826-7661; Seelos, Klaus ORCID: https://orcid.org/0009-0009-0350-1293; Zimmermann, Hanna ORCID: https://orcid.org/0000-0002-1476-3477; Haas, Jürgen ORCID: https://orcid.org/0000-0002-2314-7465; Wildemann, Brigitte ORCID: https://orcid.org/0000-0002-5389-3338; Kümpfel, Tania ORCID: https://orcid.org/0000-0001-7509-5268; Dornmair, Klaus ORCID: https://orcid.org/0000-0003-0342-5373; Korn, Thomas ORCID: https://orcid.org/0000-0002-3633-0955; Hohlfeld, Reinhard ORCID: https://orcid.org/0000-0002-6302-1488; Kerschensteiner, Martin ORCID: https://orcid.org/0000-0003-4898-9383; Gerdes, Lisa Ann ORCID: https://orcid.org/0000-0002-7053-3924 und Beltrán, Eduardo ORCID: https://orcid.org/0000-0002-7266-4098
(2024):
Twin study identifies early immunological and metabolic dysregulation of CD8 + T cells in multiple sclerosis.
In: Science Immunology, Vol. 9, No. 99, eadj8094
Abstract
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 Type: | Journal article |
|---|---|
| Faculties: | Medicine Medicine > Munich Cluster for Systems Neurology (SyNergy) Medicine > Medical Center of the University of Munich > Neurological Clinic and Polyclinic with Friedrich Baur Institute Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Psychiatry and Psychotherapy Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Radiology |
| Research Centers: | Munich Center for Neurosciences – Brain & Mind |
| Subjects: | 600 Technology > 610 Medicine and health |
| ISSN: | 2470-9468 |
| Language: | English |
| Item ID: | 123229 |
| Date Deposited: | 19. Dec 2024 07:44 |
| Last Modified: | 19. Dec 2024 07:44 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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