Neuroimmune communication at the borders of the brain

The concept of a central nervous system (CNS) border originates from the late 19th century work of Paul Ehrlich and Edwin Goldman showing that water-soluble dyes injected into the blood were unable to infiltrate the brain. Nearly 70 years later, Sir Peter Medawar performed the historic skin engraftment experiments in which it was concluded the brain was “immune privileged.” In the decades following these discoveries, advancing research has sculpted the understanding of the multidirectional communication between the CNS, its surrounding peripheral tissues, and the immune system. The notion of the brain as an “immune-privileged” organ isolated from the periphery by the blood-brain barrier (BBB) has since been refined. As will be discussed in this issue, the CNS is encompassed by multiple barriers beyond the BBB including the meninges, circumventricular organs (CVOs), and choroid plexus (ChP), all of which facilitate neuroimmune interactions to maintain CNS homeostasis as well as function as critical sites where the balance of immune surveillance is tipped to neuroinflammation.