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Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis

By David Schafflick, Chenling Xu, Maike Hartlehnert, Michael Cole, Tobias Lautwein, Andreas Schulte-Mecklenbeck, Jolien Wolbert, Michael Heming, Sven G. Meuth, Tanja Kuhlmann, Catharina Gross, Heinz Wiendl, Nir Yosef, Gerd Meyer zu Hörste

Posted 29 Aug 2018
bioRxiv DOI: 10.1101/403527 (published DOI: 10.1038/s41467-019-14118-w)

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.

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