RT Journal Article
SR Electronic
T1 Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 403527
DO 10.1101/403527
A1 David Schafflick
A1 Chenling A. Xu
A1 Maike Hartlehnert
A1 Michael Cole
A1 Tobias Lautwein
A1 Andreas Schulte-Mecklenbeck
A1 Jolien Wolbert
A1 Michael Heming
A1 Sven G. Meuth
A1 Tanja Kuhlmann
A1 Catharina C. Gross
A1 Heinz Wiendl
A1 Nir Yosef
A1 Gerd Meyer zu Horste
YR 2019
UL http://biorxiv.org/content/early/2019/04/23/403527.abstract
AB 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.