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

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...

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Published inNature communications Vol. 11; no. 1; pp. 247 - 14
Main Authors Schafflick, David, Xu, Chenling A., Hartlehnert, Maike, Cole, Michael, Schulte-Mecklenbeck, Andreas, Lautwein, Tobias, Wolbert, Jolien, Heming, Michael, Meuth, Sven G., Kuhlmann, Tanja, Gross, Catharina C., Wiendl, Heinz, Yosef, Nir, Meyer zu Horste, Gerd
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 14.01.2020
Nature Publishing Group
Nature Portfolio
Subjects
49/91
631/250/1619/554/1898/1270
631/250/38
692/53
692/699/249/1313/1666
Animal models
Animals
Autoimmune diseases
B-Lymphocytes - immunology
Blood
Blood Cells - metabolism
Central nervous system
Central Nervous System - immunology
Cerebrospinal fluid
Cerebrospinal Fluid - immunology
Composition
Cytotoxicity
Encephalomyelitis, Autoimmune, Experimental - immunology
Gene expression
Gene Expression Profiling
Helper cells
Humanities and Social Sciences
Humans
Interrogation
Leukocytes
Leukocytes - immunology
Leukocytes - metabolism
Lymphocytes
Mice
Monocytes
multidisciplinary
Multiple sclerosis
Multiple Sclerosis - blood
Multiple Sclerosis - cerebrospinal fluid
Multiple Sclerosis - immunology
Phenotype
Phenotypes
Science
Science (multidisciplinary)
Single-Cell Analysis
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
T-Lymphocytes, Helper-Inducer - immunology
T-Lymphocytes, Helper-Inducer - metabolism
Transcription
Online AccessGet full text
ISSN2041-1723
2041-1723
DOI10.1038/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. Here the authors provide a single-cell characterization of cerebrospinal fluid and blood of newly diagnosed multiple sclerosis (MS) patients, revealing altered composition of lymphocyte and monocyte subsets, validated by other methods including the interrogation of the TFH subset in mouse models of MS.
AbstractList 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.
Here the authors provide a single-cell characterization of cerebrospinal fluid and blood of newly diagnosed multiple sclerosis (MS) patients, revealing altered composition of lymphocyte and monocyte subsets, validated by other methods including the interrogation of the TFH subset in mouse models of MS.
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.Here the authors provide a single-cell characterization of cerebrospinal fluid and blood of newly diagnosed multiple sclerosis (MS) patients, revealing altered composition of lymphocyte and monocyte subsets, validated by other methods including the interrogation of the TFH subset in mouse models of MS.
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. Here the authors provide a single-cell characterization of cerebrospinal fluid and blood of newly diagnosed multiple sclerosis (MS) patients, revealing altered composition of lymphocyte and monocyte subsets, validated by other methods including the interrogation of the TFH subset in mouse models of MS.
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.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.
ArticleNumber 247
Author Hartlehnert, Maike
Heming, Michael
Kuhlmann, Tanja
Meuth, Sven G.
Lautwein, Tobias
Cole, Michael
Schulte-Mecklenbeck, Andreas
Xu, Chenling A.
Gross, Catharina C.
Meyer zu Horste, Gerd
Wiendl, Heinz
Wolbert, Jolien
Yosef, Nir
Schafflick, David
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/31937773$$D View this record in MEDLINE/PubMed
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SSID ssj0000391844
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Snippet Cerebrospinal fluid (CSF) protects the central nervous system (CNS) and analyzing CSF aids the diagnosis of CNS diseases, but our understanding of CSF...
Here the authors provide a single-cell characterization of cerebrospinal fluid and blood of newly diagnosed multiple sclerosis (MS) patients, revealing altered...
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unpaywall
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SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 247
SubjectTerms 49/91
631/250/1619/554/1898/1270
631/250/38
692/53
692/699/249/1313/1666
Animal models
Animals
Autoimmune diseases
B-Lymphocytes - immunology
Blood
Blood Cells - metabolism
Central nervous system
Central Nervous System - immunology
Cerebrospinal fluid
Cerebrospinal Fluid - immunology
Composition
Cytotoxicity
Encephalomyelitis, Autoimmune, Experimental - immunology
Gene expression
Gene Expression Profiling
Helper cells
Humanities and Social Sciences
Humans
Interrogation
Leukocytes
Leukocytes - immunology
Leukocytes - metabolism
Lymphocytes
Mice
Monocytes
multidisciplinary
Multiple sclerosis
Multiple Sclerosis - blood
Multiple Sclerosis - cerebrospinal fluid
Multiple Sclerosis - immunology
Phenotype
Phenotypes
Science
Science (multidisciplinary)
Single-Cell Analysis
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
T-Lymphocytes, Helper-Inducer - immunology
T-Lymphocytes, Helper-Inducer - metabolism
Transcription
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Title Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis
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