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

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

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May 15, 2019

Received Date 23rd April 19

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.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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Nature Communications

Nature Research, Springer Nature