Towards an Understanding of Microglia and Border-Associated Macrophages

SIMPLE SUMMARY: In the central nervous system, immune cells can be broadly categorized as parenchymal microglia or non-parenchymal border-associated macrophages. It has become increasingly evident in recent years that these cells have unique functions beyond their roles in inflammatory responses under pathological conditions. Investigating these cells can provide valuable insights into how microglia and macrophages regulate brain function throughout life, including developmental, homeostatic, aging, and disease states. Here, we provide a comprehensive overview of the current understanding of these cells in the brain. ABSTRACT: The central nervous system (CNS) plays a crucial role in regulating bodily functions by sensing and integrating environmental cues and maintaining proper physiological conditions. Recent research has revealed that CNS functions are closely coordinated with the immune system. As even minor disturbances of the immune system in the CNS can lead to various dysfunctions, diseases, or even death, it is highly specialized and segregated from that in peripheral regions. Microglia in the parenchyma and macrophages at the interface between the CNS and peripheral regions are essential immune cells in the CNS that monitor environmental changes. Recent omics analyses have revealed that these cells exhibit highly heterogeneous populations. In this review, we summarize the functions and diversity of microglia in the brain parenchyma and those of macrophages in the border regions, such as the meninges, perivascular spaces, and choroid plexus.