Scientists uncover hidden ‘gatekeeper’ cells that help protect the brain, CNS

A Vlaams Institute of Biotechnology–Ghent University Center for Inflammation Research team has identified a previously unknown cellular barrier within the choroid plexus which clarifies how the brain protects itself and reveals how systemic inflammation can disrupt this defence

Scientists at Vlaams Institute of Biotechnology–Ghent University (VIB-GU) have identified and characterised a previously unknown cellular barrier in the brain, which provides fresh insight into how the central nervous system (CNS) protects itself from the rest of the body. The study has also revealed a pathway through which the immune system can influence the brain under inflammatory conditions.

The brain depends on a series of specialised interfaces to preserve a stable internal environment. These structures regulate the passage of nutrients, metabolites and signalling molecules while they restrict access to pathogens and harmful substances. The blood–brain barrier has long been recognised as the most prominent of these protective systems. Another important interface, however, lies within the choroid plexus – the brain’s fluid-filled cavities – which is a highly vascularised structure producing cerebrospinal fluid.

Despite its physiological importance, researchers have understood remarkably little about the precise cellular architecture of the choroid plexus and the mechanisms it uses to protect the brain. Investigators from the VIB-GU Center for Inflammation Research have now undertaken a detailed anatomical and molecular analysis.

Using advanced gene sequencing and high-resolution microscopy, the team identified a distinct population of cells at the base of the choroid plexus. They termed these cells ‘base barrier cells’. The cells form tight junctions – specialised protein complexes that act as molecular rivets to seal neighbouring cells together. In effect, they create a continuous cellular sheet that separates compartments within the choroid plexus and establishes an additional layer of control between blood, cerebrospinal fluid and brain tissue.

“This discovery revealed a new line of defence for the brain,” said Professor Roosmarijn Vandenbroucke of the VIB-GU Center for Inflammation Research.

“These cells formed a dynamic and responsive gate at a location that had not been fully appreciated. The findings addressed a fundamental anatomical question and also identified a potential target to investigate brain disorders,” she added.

Functional experiments demonstrated that the barrier was not a static wall. Under healthy physiological conditions, the base barrier cells restricted the movement of even small molecules from the blood-rich core of the choroid plexus into the surrounding cerebrospinal fluid and adjacent brain tissue. This selective permeability reinforced the concept that the choroid plexus does not merely produce cerebrospinal fluid but also regulates its composition with considerable precision.

However, the researchers observed that systemic inflammation altered this balance. During inflammatory states, such as those triggered by severe infection, the integrity of the base barrier weakened. Structural changes in the tight junctions reduced the sealing capacity of the cellular layer.

“We observed that the base barrier cells became vulnerable during systemic inflammation, which could permit harmful substances or immune cells to enter the CNS,” said Dr Daan Verhaege, who completed his doctoral research in the Vandenbroucke laboratory.

This finding carries implications beyond basic neuroanatomy. The CNS has often been described as immune-privileged, yet increasing evidence indicates that peripheral immune signals can influence brain function and contribute to neurological disease. The identification of base barrier cells offers a tangible anatomical route through which inflammatory signals may gain access to the brain.

Developmental analysis showed that the base barrier emerges early in embryonic life and persists into adulthood. The researchers confirmed its presence in both mouse and human brain tissue which strengthens the relevance of its discovery to human health. The conservation of this structure across species suggests that it fulfils an essential biological function.

The work therefore reframes the choroid plexus as more than a passive producer of cerebrospinal fluid. It represents an active immunological interface that can both protect and – under pathological conditions – expose the brain. Disorders such as multiple sclerosis, meningitis and certain neurodegenerative diseases have long been associated with inflammation and barrier dysfunction. A clearer understanding of this additional barrier may help to explain how peripheral inflammation contributes to central pathology.

Professor Vandenbroucke said the findings had highlighted both the vulnerability and the protectability of the brain. She added that targeted strategies to reinforce this gatekeeper layer might, in future, form part of therapeutic approaches designed to limit neuroinflammation or to modulate immune access to the brain.

The identification of base barrier cells underscores how even well-studied organs can still yield fundamental anatomical surprises. It also illustrates the importance of precise cellular mapping to understand disease mechanisms. By charting this previously unrecognised interface, the team has provided a framework to explore how immune signals traverse the boundary between body and brain.

For further reading please visit: 10.1038/s41593-025-02188-7