1. Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis.
- Author
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Schafflick D, Xu CA, Hartlehnert M, Cole M, Schulte-Mecklenbeck A, Lautwein T, Wolbert J, Heming M, Meuth SG, Kuhlmann T, Gross CC, Wiendl H, Yosef N, and Meyer Zu Horste G
- Subjects
- Animals, B-Lymphocytes immunology, Blood Cells metabolism, Central Nervous System immunology, Encephalomyelitis, Autoimmune, Experimental immunology, Gene Expression Profiling, Humans, Leukocytes metabolism, Mice, Multiple Sclerosis blood, Multiple Sclerosis cerebrospinal fluid, Phenotype, Single-Cell Analysis, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Helper-Inducer metabolism, Cerebrospinal Fluid immunology, Leukocytes immunology, Multiple Sclerosis immunology
- Abstract
Cerebrospinal fluid (CSF) protects the central nervous system (CNS) and analyzing CSF aids the diagnosis of CNS diseases, but our understanding of CSF leukocytes remains superficial. Here, using single cell transcriptomics, we identify a specific location-associated composition and transcriptome of CSF leukocytes. Multiple sclerosis (MS) - an autoimmune disease of the CNS - increases transcriptional diversity in blood, but increases cell type diversity in CSF including a higher abundance of cytotoxic phenotype T helper cells. An analytical approach, named cell set enrichment analysis (CSEA) identifies a cluster-independent increase of follicular (TFH) cells potentially driving the known expansion of B lineage cells in the CSF in MS. In mice, TFH cells accordingly promote B cell infiltration into the CNS and the severity of MS animal models. Immune mechanisms in MS are thus highly compartmentalized and indicate ongoing local T/B cell interaction.
- Published
- 2020
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