Base barrier cells provide compartmentalization of choroid plexus, brain and CSF

The choroid plexus (ChP), located in the brain ventricles, is largely composed of ChP epithelial cells that produce the cerebrospinal fluid (CSF) and form the blood–CSF barrier. At the ChP–brain attachment sites, we have discovered unique fibroblasts referred to as ChP base barrier cells (BBCs). We show that ChP BBCs originate from meningeal mesenchymal precursors, arrive early during development, remain throughout life and are conserved across species. ChP BBCs are transcriptionally similar to meningeal arachnoid barrier cells and are interconnected by both adherens and tight junctions. Notably, we provide evidence that the BBCs function as a barrier, controlling communication between the periphery and central nervous system. Moreover, during inflammatory insult, we observed a loss of barrier integrity and immune cell crossing. Altogether, our research revealed a barrier at the ChP base, crucial in protecting the central nervous system by compartmentalizing the ChP stroma, brain parenchyma and CSF. Verhaege et al. identify a conserved fibroblast barrier population at the base of the choroid plexus that compartmentalizes brain–CSF interfaces and is disrupted by inflammation, revealing a new site of central nervous system immune entry and barrier regulation.