CD163+ macrophages monitor enhanced permeability at the blood-dorsal root ganglion barrier
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Updated: Jul 8, 2025
Rapid Isolation of Dorsal Root Ganglion Macrophages
Published on: September 7, 2019
Harald Lund1, Matthew A Hunt1, Zerina Kurtović1,2
1Department of Physiology and Pharmacology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Abstract:
In dorsal root ganglia (DRG), macrophages reside close to sensory neurons and have largely been explored in the context of pain, nerve injury, and repair. However, we discovered that most DRG macrophages interact with and monitor the vasculature by sampling macromolecules from the blood. Characterization of the DRG vasculature revealed a specialized endothelial bed that transformed in molecular, structural, and permeability properties along the arteriovenous axis and was covered by macrophage-interacting pericytes and fibroblasts. Macrophage phagocytosis spatially aligned with peak endothelial permeability, a process regulated by enhanced caveolar transcytosis in endothelial cells. Profiling the DRG immune landscape revealed two subsets of perivascular macrophages with distinct transcriptome, turnover, and function. CD163+ macrophages self-maintained locally, specifically participated in vasculature monitoring, displayed distinct responses during peripheral inflammation, and were conserved in mouse and man. Our work provides a molecular explanation for the permeability of the blood-DRG barrier and identifies an unappreciated role of macrophages as integral components of the DRG-neurovascular unit.
Insights
Dorsal root ganglia (DRG) macrophages primarily monitor blood vessels, not just nerve repair. These macrophages, particularly CD163+ cells, are key to understanding the blood-DRG barrier and neurovascular unit function.
Area of Science:
- Neuroscience
- Immunology
- Vascular Biology
Background:
- Macrophages in dorsal root ganglia (DRG) are traditionally studied for roles in nerve injury and pain.
- Their interaction with the DRG vasculature remains largely unexplored.
Purpose of the Study:
- To investigate the role of DRG macrophages in monitoring the DRG vasculature.
- To characterize the specialized nature of the DRG blood-DRG barrier.
- To identify macrophage subsets within the DRG and their functions.
Main Methods:
- Characterization of DRG vasculature and endothelial cells.
- Analysis of macrophage interactions with the vasculature.
- Transcriptomic profiling of DRG immune cells.
- Investigation of macrophage subsets (CD163+) and their behavior during inflammation.
Main Results:
- Most DRG macrophages sample macromolecules from the blood, indicating a role in vasculature monitoring.
- The DRG vasculature exhibits specialized endothelial permeability regulated by caveolar transcytosis.
- Two distinct perivascular macrophage subsets were identified, including CD163+ macrophages with self-maintenance and vasculature-monitoring roles.
- CD163+ macrophage functions and responses during inflammation are conserved across species.
Conclusions:
- Macrophages are integral components of the DRG-neurovascular unit, actively monitoring the blood-DRG barrier.
- The study provides a molecular basis for blood-DRG barrier permeability.
- Identifies a novel, conserved role for CD163+ macrophages in vasculature surveillance within the DRG.
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