Extrasinusoidal macrophages are a distinct subset of immunologically active dural macrophages
Lukas Amann, A Fell, Gianni Monaco, Roman Sankowski, Hao Wu, Marta Joana Costa Jordão, Katharina Borst, Maximilian Fliegauf, Takahiro Masuda, Alberto Ardura-Fabregat, Neil Paterson, Elisa Nent, James Cook, Ori Staszewski, Omar Mossad, Thorsten Falk, Antoine Louveau, Igor Smirnov, Jonathan Kipnis, Tim Lämmermann, Marco Prinz
Abstract
Although macrophages in the meningeal compartments of the central nervous system (CNS) have been comprehensively characterized under steady state, studying their contribution to physiological and pathological processes has been hindered by the lack of specific targeting tools in vivo. Recent findings have shown that the dural sinus and its adjacent lymphatic vessels act as a neuroimmune interface. However, the cellular and functional heterogeneity of extrasinusoidal dural macrophages outside this immune hub is not fully understood. Therefore, we comprehensively characterized these cells using single-cell transcriptomics, fate mapping, confocal imaging, clonal analysis, and transgenic mouse lines. Extrasinusoidal dural macrophages were distinct from leptomeningeal and CNS parenchymal macrophages in terms of their origin, expansion kinetics, and transcriptional profiles. During autoimmune neuroinflammation, extrasinusoidal dural macrophages performed efferocytosis of apoptotic granulocytes. Our results highlight a previously unappreciated myeloid cell diversity and provide insights into the brain's innate immune system.