Extrasinusoidal macrophages are a distinct subset of immunologically active dural macrophages
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.
Authors
- Omar Mossad (ORCID: https://orcid.org/0000-0003-4329-7804)
- Maximilian Fliegauf (ORCID: https://orcid.org/0000-0002-3787-0427)
- Roman Sankowski (ORCID: https://orcid.org/0000-0001-9215-8021)
- Elisa Nent
- Marco Prinz (ORCID: https://orcid.org/0000-0002-0349-1955)
- Antoine Louveau (ORCID: https://orcid.org/0000-0003-2094-2735)
- Katharina Borst
- Tim Lämmermann (ORCID: https://orcid.org/0000-0002-8553-118X)
- Neil Paterson (ORCID: https://orcid.org/0000-0001-9563-5874)
- Takahiro Masuda (ORCID: https://orcid.org/0000-0003-3687-452X)
- A Fell (ORCID: https://orcid.org/0009-0000-8880-3702)
- Gianni Monaco (ORCID: https://orcid.org/0000-0002-7863-4068)
- Thorsten Falk (ORCID: https://orcid.org/0000-0001-8612-3201)
- James Cook (ORCID: https://orcid.org/0000-0002-1905-4928)
- Igor Smirnov (ORCID: https://orcid.org/0000-0003-2373-6742)
- Lukas Amann (ORCID: https://orcid.org/0000-0002-8363-373X)
- Ori Staszewski (ORCID: https://orcid.org/0000-0002-0579-6701)
- Marta Joana Costa Jordão (ORCID: https://orcid.org/0000-0001-7888-2195)
- Jonathan Kipnis (ORCID: https://orcid.org/0000-0002-3714-517X)
- Alberto Ardura-Fabregat (ORCID: https://orcid.org/0000-0003-1134-4047)
- Hao Wu
Institutions
- Kyushu University (JP)
- University of Freiburg (DE)
- Washington University in St. Louis (US)
- Cleveland Clinic Lerner College of Medicine (US)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- Institute of Molecular Biology (DE)
- University of Virginia (US)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-12-20
- DOI
- https://doi.org/10.1126/sciimmunol.adh1129
- Citations
- 19
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 4.70