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

Autor: Kavaka V; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany., Mutschler L; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany., de la Rosa Del Val C; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany.; Graduate School of Systemic Neurosciences, Ludwig Maximilian University of Munich, Munich, Germany., Eglseer K; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany., Gómez Martínez AM; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany., Flierl-Hecht A; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany.; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany., Ertl-Wagner B; Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Department of Medical Imaging, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada., Keeser D; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Mortazavi M; Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Seelos K; Institute of Neuroradiology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Zimmermann H; Institute of Neuroradiology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Haas J; Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany., Wildemann B; Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany., Kümpfel T; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany.; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany., Dornmair K; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany.; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany., Korn T; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.; Institute for Experimental Neuroimmunology, Technical University of Munich School of Medicine, Munich, Germany.; Department of Neurology, Technical University of Munich School of Medicine, Munich, Germany., Hohlfeld R; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany.; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany., Kerschensteiner M; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany.; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany., Gerdes LA; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany.; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany., Beltrán E; Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University of Munich, Martinsried, Germany.; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2024 Sep 27; Vol. 9 (99), pp. eadj8094. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1126/sciimmunol.adj8094
Abstrakt: 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.
Databáze: MEDLINE