Specification of CNS macrophage subsets occurs postnatally in defined niches

Takahiro Masuda, Lukas Amann, Gianni Monaco, Roman Sankowski, Ori Staszewski, Martin Krueger, Francesca Del Gaudio, Liqun He, Neil Paterson, Elisa Nent, Francisco Fernández-Klett, Ayato Yamasaki, Maximilian Frosch, Maximilian Fliegauf, Lance Fredrick Pahutan Bosch, Hatice Ulupinar, Nora Hagemeyer, Dietmar Schreiner, Cayce Dorrier, Makoto TsudaClaudia Grothe, Anne Joutel, Richard Daneman, Christer Betsholtz, Urban Lendahl, Klaus Peter Knobeloch, Tim Lämmermann, Josef Priller, Katrin Kierdorf, Marco Prinz

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

All tissue-resident macrophages of the central nervous system (CNS)—including parenchymal microglia, as well as CNS-associated macrophages (CAMs1) such as meningeal and perivascular macrophages2–7—are part of the CNS endogenous innate immune system that acts as the first line of defence during infections or trauma2,8–10. It has been suggested that microglia and all subsets of CAMs are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors11–15. However, the precise ontogenetic relationships, the underlying transcriptional programs and the molecular signals that drive the development of distinct CAM subsets in situ are poorly understood. Here we show, using fate-mapping systems, single-cell profiling and cell-specific mutants, that only meningeal macrophages and microglia share a common prenatal progenitor. By contrast, perivascular macrophages originate from perinatal meningeal macrophages only after birth in an integrin-dependent manner. The establishment of perivascular macrophages critically requires the presence of arterial vascular smooth muscle cells. Together, our data reveal a precisely timed process in distinct anatomical niches for the establishment of macrophage subsets in the CNS.

Original languageEnglish
Pages (from-to)740-748
Number of pages9
JournalNature
Volume604
Issue number7907
DOIs
Publication statusPublished - Apr 28 2022

All Science Journal Classification (ASJC) codes

  • General

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