The choroid plexus synergizes with immune cells during neuroinflammation

The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use longitudinal two-photon imaging in awake mice and single-cell transcriptomics to elucidate the mechanisms of ChP regulation of brain inflammation. We used intracerebroventricular injections of lip...

Full description

Saved in:

Bibliographic Details
Published in:	Cell Vol. 187; no. 18; p. 4946
Main Authors:	Xu, Huixin, Lotfy, Peter, Gelb, Sivan, Pragana, Aja, Hehnly, Christine, Byer, Lillian I J, Shipley, Frederick B, Zawadzki, Miriam E, Cui, Jin, Deng, Liwen, Taylor, Milo, Webb, Mya, Lidov, Hart G W, Andermann, Mark L, Chiu, Isaac M, Ordovas-Montanes, Jose, Lehtinen, Maria K
Format:	Journal Article
Language:	English
Published:	United States 05-09-2024
Subjects:	Animals Blood-Brain Barrier - metabolism Choroid Plexus - metabolism Epithelial Cells - metabolism Female Lipopolysaccharides Macrophages - immunology Macrophages - metabolism Male Mice Mice, Inbred C57BL Monocytes - metabolism Neuroinflammatory Diseases - metabolism Neutrophils - immunology Neutrophils - metabolism Tight Junctions - metabolism epiplexus macrophages adhesion molecules colony-stimulating factor 1 neuroinflammation immune recruitment epithelial cells blood-CSF barrier bacterial infection choroid plexus
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use longitudinal two-photon imaging in awake mice and single-cell transcriptomics to elucidate the mechanisms of ChP regulation of brain inflammation. We used intracerebroventricular injections of lipopolysaccharides (LPS) to model meningitis in mice and observed that neutrophils and monocytes accumulated in the ChP stroma and surged across the epithelial barrier into the CSF. Bi-directional recruitment of monocytes from the periphery and, unexpectedly, macrophages from the CSF to the ChP helped eliminate neutrophils and repair the barrier. Transcriptomic analyses detailed the molecular steps accompanying this process and revealed that ChP epithelial cells transiently specialize to nurture immune cells, coordinating their recruitment, survival, and differentiation as well as regulation of the tight junctions that control the permeability of the ChP brain barrier. Collectively, we provide a mechanistic understanding and a comprehensive roadmap of neuroinflammation at the ChP brain barrier.
ISSN:	1097-4172
DOI:	10.1016/j.cell.2024.07.002