Language

English

Publication Date

3-1-2026

Journal

Nature Neuroscience

DOI

10.1038/s41593-025-02158-z

PMID

41566006

PMCID

PMC13178392

PubMedCentral® Posted Date

7-21-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

The choroid plexus forms a key barrier and signaling interface between the brain and peripheral circulation, yet its immune landscape remains incompletely understood. Using single-cell transcriptomics combined with lineage and spatial tracing methods, we identified three biologically distinct populations of choroid plexus macrophages, defined by differential expression of CD163, MHCII or CD9. These subsets arise from separate hematopoietic waves, occupy distinct anatomical niches and differentially rely on CSF1 and IL-34 for survival. We found that TGFβ signaling is essential to maintain their tissue-specific identities, and deletion of Tgfbr2 in these cells induces broad phenotypic reprogramming. During neuroinflammation, choroid plexus macrophages mount type I interferon responses and secrete chemokines that recruit CD8+ T cells. Finally, analysis of human choroid plexus reveals macrophage subsets corresponding to those found in mice, indicating evolutionary conservation of their molecular and immune features. Together, these findings define the developmental origin, niche specialization and immune dynamics of choroid plexus macrophages.

Keywords

Animals, Choroid Plexus, Macrophages, Mice, Humans, Receptor, Transforming Growth Factor-beta Type II, Mice, Inbred C57BL, Female, Signal Transduction

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.