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

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. Gross; Heinz Wiendl; Nir Yosef; Gerd Meyer zu Horste

doi:https://doi.org/10.1038/s41467-019-14118-w

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

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. Gross, Heinz Wiendl, Nir Yosef, Gerd Meyer zu Horste

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	247
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-14118-w
State	Published - 1 Dec 2020
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Schafflick, D., Xu, C. A., Hartlehnert, M., Cole, M., Schulte-Mecklenbeck, A., Lautwein, T., Wolbert, J., Heming, M., Meuth, S. G., Kuhlmann, T., Gross, C. C., Wiendl, H., Yosef, N., & Meyer zu Horste, G. (2020). Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis. Nature Communications, 11(1), Article 247. https://doi.org/10.1038/s41467-019-14118-w

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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.",

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

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Schafflick, D, Xu, CA, Hartlehnert, M, Cole, M, Schulte-Mecklenbeck, A, Lautwein, T, Wolbert, J, Heming, M, Meuth, SG, Kuhlmann, T, Gross, CC, Wiendl, H, Yosef, N & Meyer zu Horste, G 2020, 'Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis', Nature Communications, vol. 11, no. 1, 247. https://doi.org/10.1038/s41467-019-14118-w

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T1 - Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis

AU - Schafflick, David

AU - Xu, Chenling A.

AU - Hartlehnert, Maike

AU - Cole, Michael

AU - Schulte-Mecklenbeck, Andreas

AU - Lautwein, Tobias

AU - Wolbert, Jolien

AU - Heming, Michael

AU - Meuth, Sven G.

AU - Kuhlmann, Tanja

AU - Gross, Catharina C.

AU - Wiendl, Heinz

AU - Yosef, Nir

AU - Meyer zu Horste, Gerd

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

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, 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.

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SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

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

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