CNS Border-Associated Macrophages: Ontogeny and Potential Implication in Disease

Being immune privileged, the central nervous system (CNS) is constituted by unique parenchymal and non-parenchymal tissue-resident macrophages, namely, microglia and border-associated macrophages (BAMs), respectively. BAMs are found in the choroid plexus, meningeal and perivascular spaces, playing critical roles in maintaining CNS homeostasis while being phenotypically and functionally distinct from microglial cells. Although the ontogeny of microglia has been largely determined, BAMs need comparable scrutiny as they have been recently discovered and have not been thoroughly explored. Newly developed techniques have transformed our understanding of BAMs, revealing their cellular heterogeneity and diversity. Recent data showed that BAMs also originate from yolk sac progenitors instead of bone marrow-derived monocytes, highlighting the absolute need to further investigate their repopulation pattern in adult CNS. Shedding light on the molecular cues and drivers orchestrating BAM generation is essential for delineating their cellular identity. BAMs are receiving more attention since they are gradually incorporated into neurodegenerative and neuroinflammatory disease evaluations. The present review provides insights towards the current understanding regarding the ontogeny of BAMs and their involvement in CNS diseases, paving their way into targeted therapeutic strategies and precision medicine.

Automated summary

The central nervous system (CNS) is immune privileged and contains unique macrophages known as microglia and border-associated macrophages (BAMs). BAMs, found in specific locations such as the choroid plexus and meningeal spaces, play crucial roles in maintaining CNS homeostasis and are distinct from microglial cells. Recent advances in technology have led to a better understanding of BAMs, including their cellular diversity and origin from yolk sac progenitors. The study of BAMs is important as they are implicated in neurodegenerative and neuroinflammatory diseases.