Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis
Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis
Summary 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, we firstly provide a transcriptional map of single leukocytes in CSF compared to blood. Leukocyte composition and transcriptome were compartment-specific with CSF-enrichment of myeloid dendritic cells and a border-associated phenotype of monocytes. We secondly tested how multiple sclerosis (MS) - an autoimmune disease of the CNS - affected both compartments. MS increased transcriptional diversity in blood, while it preferentially increased cell type diversity in CSF. In addition to the known expansion of B lineage cells, we identified an increase of cytotoxic-phenotype and follicular T helper (TFH) cells in the CSF. In mice, TFH cells accordingly promoted B cell infiltration into the CNS and severity of MS animal models. Immune mechanisms in MS are thus highly compartmentalized and indicate local T/B cell interaction.
Schulte-Mecklenbeck Andreas、Horste Gerd Meyer zu、Kuhlmann Tanja、Gross Catharina C.、Yosef Nir、Schafflick David、Cole Michael、Lautwein Tobias、Meuth Sven G.、Xu Chenling A.、Hartlehnert Maike、Wiendl Heinz、Wolbert Jolien、Heming Michael
Department of Neurology with Institute of Translational Neurology, University Hospital M¨1nsterDepartment of Neurology with Institute of Translational Neurology, University Hospital M¨1nsterInstitute of Neuropathology, University Hospital M¨1nsterDepartment of Neurology with Institute of Translational Neurology, University Hospital M¨1nsterDepartment of Electrical Engineering & Computer Science, Center for Computational Biology, University of California||Ragon Institute of MGH, MIT and Harvard||Chan Zuckerberg BiohubDepartment of Neurology with Institute of Translational Neurology, University Hospital M¨1nsterDepartment of Physics, University of California||Department of Electrical Engineering & Computer Science, Center for Computational Biology, University of CaliforniaDepartment of Neurology with Institute of Translational Neurology, University Hospital M¨1nsterDepartment of Neurology with Institute of Translational Neurology, University Hospital M¨1nsterDepartment of Electrical Engineering & Computer Science, Center for Computational Biology, University of CaliforniaDepartment of Neurology with Institute of Translational Neurology, University Hospital M¨1nsterDepartment of Neurology with Institute of Translational Neurology, University Hospital M¨1nsterDepartment of Neurology with Institute of Translational Neurology, University Hospital M¨1nsterDepartment of Neurology with Institute of Translational Neurology, University Hospital M¨1nster
神经病学、精神病学基础医学细胞生物学
transcriptomicssingle-cell RNA-seqcerebrospinal fluidmultiple sclerosisT follicular helper cellsexperimental autoimmune encephalomyelitis
Schulte-Mecklenbeck Andreas,Horste Gerd Meyer zu,Kuhlmann Tanja,Gross Catharina C.,Yosef Nir,Schafflick David,Cole Michael,Lautwein Tobias,Meuth Sven G.,Xu Chenling A.,Hartlehnert Maike,Wiendl Heinz,Wolbert Jolien,Heming Michael.Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/403527.点此复制
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