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

Author

Listed:
  • David Schafflick

    (University Hospital Münster)

  • Chenling A. Xu

    (University of California)

  • Maike Hartlehnert

    (University Hospital Münster)

  • Michael Cole

    (University of California
    University of California)

  • Andreas Schulte-Mecklenbeck

    (University Hospital Münster)

  • Tobias Lautwein

    (University Hospital Münster)

  • Jolien Wolbert

    (University Hospital Münster)

  • Michael Heming

    (University Hospital Münster)

  • Sven G. Meuth

    (University Hospital Münster)

  • Tanja Kuhlmann

    (University Hospital Münster)

  • Catharina C. Gross

    (University Hospital Münster)

  • Heinz Wiendl

    (University Hospital Münster)

  • Nir Yosef

    (University of California
    MIT and Harvard
    Chan Zuckerberg Biohub)

  • Gerd Meyer zu Horste

    (University Hospital Münster)

Abstract

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, using single cell transcriptomics, we identify a specific location-associated composition and transcriptome of CSF leukocytes. Multiple sclerosis (MS) – an autoimmune disease of the CNS – increases transcriptional diversity in blood, but increases cell type diversity in CSF including a higher abundance of cytotoxic phenotype T helper cells. An analytical approach, named cell set enrichment analysis (CSEA) identifies a cluster-independent increase of follicular (TFH) cells potentially driving the known expansion of B lineage cells in the CSF in MS. In mice, TFH cells accordingly promote B cell infiltration into the CNS and the severity of MS animal models. Immune mechanisms in MS are thus highly compartmentalized and indicate ongoing local T/B cell interaction.

Suggested Citation

  • David Schafflick & Chenling A. Xu & Maike Hartlehnert & Michael Cole & Andreas Schulte-Mecklenbeck & Tobias Lautwein & Jolien Wolbert & Michael Heming & Sven G. Meuth & Tanja Kuhlmann & Catharina C. G, 2020. "Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14118-w
    DOI: 10.1038/s41467-019-14118-w
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