Transcriptomics

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


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 co-twin had either no or subclinical neuroinflammation (SCNI). We identified peripheral MS-associated immunological and metabolic alterations indicative of an enhanced migratory, pro-inflammatory, and activated CD8+ T cell phenotype, which was also evident in co-twins with SCNI and in an independent validation cohort of people with MS (pwMS). Together, our in-depth single-cell analysis indicates a disease-driving pro-inflammatory role of infiltrating CD8+ T cells and identifies potential immunological and metabolic therapeutic targets in both prodromal and definitive stages of the disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE276167 | GEO | 2024/09/26

REPOSITORIES: GEO

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