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Single cell transcriptomics identifies an MS-specific composition and expression of cerebrospinal fluid cells
Author(s): ,
D. Schafflick
Affiliations:
Department of Neurology with Institute of Translational Neurology, University Clinic Münster, Münster, Germany
,
M. Hartlehnert
Affiliations:
Department of Neurology with Institute of Translational Neurology, University Clinic Münster, Münster, Germany
,
M. Cole
Affiliations:
Department of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA, United States
,
T. Lautwein
Affiliations:
Department of Neurology with Institute of Translational Neurology, University Clinic Münster, Münster, Germany
,
J. Wolbert
Affiliations:
Department of Neurology with Institute of Translational Neurology, University Clinic Münster, Münster, Germany
,
C.C. Gross
Affiliations:
Department of Neurology with Institute of Translational Neurology, University Clinic Münster, Münster, Germany
,
S. Meuth
Affiliations:
Department of Neurology with Institute of Translational Neurology, University Clinic Münster, Münster, Germany
,
N. Yosef
Affiliations:
Department of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA, United States
,
H. Wiendl
Affiliations:
Department of Neurology with Institute of Translational Neurology, University Clinic Münster, Münster, Germany
G. Meyer zu Hörste
Affiliations:
Department of Neurology with Institute of Translational Neurology, University Clinic Münster, Münster, Germany
ECTRIMS Online Library. Meyer zu Hörste G. Oct 12, 2018; 228922; P1081
Gerd Meyer zu Hörste
Gerd Meyer zu Hörste
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Abstract: P1081

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Immunology

The central nervous system (CNS) is ensheathed by cerebrospinal fluid (CSF) that is constantly circulated by immune cells and provides protection and immune surveillance. CSF is routinely sampled to diagnose neurological disorders and allows studying local immune reactions in the vicinity of the CNS but our understanding of CSF cells is limited. We employed microfluidics-based single cell RNA-sequencing (scRNA-seq) and RNA-seq of sorted CSF cells to study fresh CSF cells from human patients with multiple sclerosis (MS) and matched controls.
We identified 10 subsets of CSF cells including diverse immune cell types. We also identified a disease-specific expansion of B lineage cells and natural killer (NK) cells. Transcriptional profiling of CSF cells identified an increased expression of activation and cytotoxicity transcripts in MS patients. In subsequent experiments we confirmed that an increase in T follicular helper (TFH) cells drives the maturation and expansion of B lineage cells in the CSF in MS. In this unbiased high-throughput transcriptional profiling of CSF cells we thus identify mechanisms driving MS-related inflammation in the CSF. This study thus sets the stage for a deeper understanding of immune surveillance and of auto-inflammation in the central nervous system.
Disclosure: D.S., M.H., M.C., T.L., J.W., N.Y. have nothing to disclose.
C.C.G: has received grants from the German Ministry for Education and Research (BMBF; 01GI1603A), the German Research Foundation (DFG; GR3946/3-1 and SFB/Transregio 128 A09), and the European Union (Horizon2020, RESTORE). She has also received speaker honoraria and travel expenses for attending meetings from Biogen, Genzyme, Novartis Pharma GmbH, and Bayer Health Care.
S.G.M. has received honoraria for lecturing, travel expenses for attending meetings and financial research support from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS and Teva.
HW: receives honoraria for acting as a member of Scientific Advisory Boards for Biogen, Sanofi-Genzyme, Merck Serono, Novartis, Evgen, MedDay Pharmaceuticals, Roche Pharma AG); speaker honoraria and travel support (Biogen, Sanofi-Genzyme, Merck Serono, Novartis, Roche Pharma AG, Alexion, Cognomed, F.Hoffmann-LA Roche Ltd, TEVA, WebMD Global, Gemeinnützige Hertie-Stiftung, Peervoice, Swiss Multiple Sclerosis Society); compensation as consultant (Biogen, Novartis, Sanofi-Genzyme, Abbvie, Actelion, IGES, GlaxoSmithKline GmbH, Roche Pharma AG, Swiss Multiple Sclerosis Society) an received research support by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Else Kröner Fresenius Foundation, Fresenius Foundation, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster and RE Children's Foundation, Biogen, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme and Novartis.
G.MzH: has received research funding from the Deutsche Forschungsgemeinschaft (DFG; ME4050/4-1), from the Gemeinnützige Hertie Stiftung,, and from the Ministerium für Innovation, Wissenschaft und Forschung (MIWF) des Landes Nordrhein-Westfalen. G.M.z.H. has received speaker honoraria from Alexion pharma and acts as a member of Scientific Advisory Boards for LFB Pharma.

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