Layered neuroimmune interfaces at CNS borders: Stress reshapes CNS immunity

In recent years, the traditional view of the central nervous system (CNS) as an immunologically isolated "immune-privileged" organ has been reconsidered. Accumulating evidence has led to recognition of the CNS as an immunologically dynamic organ that closely interacts with immune cells and immune-related structures. Together, these advances suggest that regions surrounding the CNS function as an immunological interface mediating interactions between the CNS and the immune system within a spatially organized and compartmentalized architecture, thereby increasing interest in immune cell dynamics at the CNS border regions. Under stress conditions, quantitative and qualitative changes in immune cells at the CNS border regions have been reported, and such alterations have been associated with changes in neural activity and behavior, although the causal relationships and underlying mechanisms remain incompletely understood. In light of the paradigm shift from immunologically isolated immune privilege to the concept of the CNS as an organ with a spatially stratified immunological interface, this review organizes current knowledge of the CNS border regions within an anatomical framework and summarizes immune cell dynamics under stress conditions, highlighting established findings and unresolved questions.