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

• Published in: Nature 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
• Language: English
• 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
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-14118-w

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.