Macrophage centripetal migration drives spontaneous healing process after spinal cord injury

Sci. Adv., 2019 · DOI: 10.1126/sciadv.aav5086 · Published: May 15, 2019

Simple Explanation

Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury.

Study Duration

Not specified

Participants

Mice

Evidence Level

Not specified

Key Findings

1
IRF8 expression is increased in the spinal cord after SCI.
2
IRF8 is selectively expressed in CD68+ cells after SCI
3
IRF8 is crucial for the epicenter-directed macrophage migration in the injured spinal cord

Research Summary

The study investigates the role of macrophages and the interferon regulatory factor 8 (IRF8) in the spontaneous healing process after spinal cord injury (SCI). The research reveals that macrophages migrate towards the lesion epicenter in a process dependent on IRF8 and the chemoattractant C5a. Activation of IRF8 signaling enhanced the migration of macrophages and functional recovery after SCI, suggesting a potential therapeutic strategy.

Practical Implications

Therapeutic Target

Macrophage centripetal migration via IRF8 provides a novel therapeutic target for central nervous system injury.

Drug Development

Pharmacological promotion of IRF8 activation facilitates macrophage centripetal movement, thereby improving the SCI recovery.

Clinical Intervention

Promoting infiltrating cell migration toward the lesion epicenter after traumatic CNS injury is a potential therapeutic strategy.

Study Limitations

1
Other molecules might be also involved in migration of macrophages in the injured spinal cord.
2
The upstream mechanisms of IRF8 activation in injured spinal cord need further investigation.
3
In vivo, microglia may have difficulty migrating because of the tight cell adhesion in the tissue after injury

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