Border-associated macrophages in the central nervous system

Abstract Tissue-resident macrophages play an important role in the local maintenance of homeostasis and immune surveillance. In the central nervous system (CNS), brain macrophages are anatomically divided into parenchymal microglia and non-parenchymal border-associated macrophages (BAMs). Among these immune cell populations, microglia have been well-studied for their roles during development as well as in health and disease. BAMs, mostly located in the choroid plexus, meningeal and perivascular spaces, are now gaining increased attention due to advancements in multi-omics technologies and genetic methodologies. Research on BAMs over the past decade has focused on their ontogeny, immunophenotypes, involvement in various CNS diseases, and potential as therapeutic targets. Unlike microglia, BAMs display mixed origins and distinct self-renewal capacity. BAMs are believed to regulate neuroimmune responses associated with brain barriers and contribute to immune-mediated neuropathology. Notably, BAMs have been observed to function in diverse cerebral pathologies, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, ischemic stroke, and gliomas. The elucidation of the heterogeneity and diverse functions of BAMs during homeostasis and neuroinflammation is mesmerizing, since it may shed light on the precision medicine that emphasizes deep insights into programming cues in the unique brain immune microenvironment. In this review, we delve into the latest findings on BAMs, covering aspects like their origins, self-renewal capacity, adaptability, and implications in different brain disorders.