Immunological Roles of Cerebrospinal Fluid

ABSTRACT Although viewed as an immune‐privileged organ for decades, there is growing awareness that the central nervous system (CNS) is in constant communication with the immune system. This neuroimmune communication occurs not within the CNS parenchyma, but instead at a series of immune‐rich border tissues: the choroid plexus, the meninges, and the skull. Facilitating this neuroimmune communication is cerebrospinal fluid (CSF). In the past decade, rapid advances have been made in CSF biology, showing that it performs waste clearance and antigen trafficking functions. CSF can directly access brain border compartments through specific anatomical sites to direct immune responses in these regions and mobilize immune cells to enter the CNS. Furthermore, the major routes of immune trafficking in the CNS lead first to the CSF, which, during inflammation, provides a hospitable environment for immune activation. Collectively, these properties make CSF not only important for the physical protection of the brain, but also for its immunology.