학술논문

Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis.
Document Type
article
Source
Nature communications. 11(1)
Subject
Animals
B-Lymphocytes
Blood Cells
Central Nervous System
Cerebrospinal Fluid
Encephalomyelitis
Autoimmune
Experimental
Gene Expression Profiling
Humans
Leukocytes
Mice
Multiple Sclerosis
Phenotype
Single-Cell Analysis
T-Lymphocyte Subsets
T-Lymphocytes
Helper-Inducer
Language
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.