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Unmasking the CNS Battleground: How Single-Cell Sequencing Revealed the Immune Drivers of Multiple Sclerosis
Unmasking the CNS Battleground: How Single-Cell Sequencing Revealed the Immune Drivers of Multiple Sclerosis

Multiple sclerosis (MS) is a complex autoimmune disease where immune cells attack the central nervous system (CNS), yet the precise actions of these cells in the CNS—specifically within the cerebrospinal fluid (CSF)—remain elusive. To gain a high-resolution understanding, researchers conducted an exploratory study utilizing cutting-edge single-cell RNA sequencing (scRNA-seq) on CSF samples from patients with relapsing–remitting MS (RRMS). This detailed map provided novel insights into the localized inflammation, revealing a significant expansion of B cells and plasma cells within the CSF compartment compared to healthy controls. Beyond this shift in composition, the analysis showed a transcriptional reprogramming of T cells, indicating altered activation states and heightened inflammatory potential. Crucially, the study also identified a reconfigured communication network centered on mononuclear phagocytes (macrophages), highlighting specific signaling pathways like the CXCL12–CXCR4 axis that may amplify CNS inflammation. While this initial analysis involved a very small cohort (3 RRMS patients) and is considered hypothesis-generating, it establishes a framework for exploring localized autoimmunity and suggests promising new targets for future, disease-specific therapies.

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