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Macrophage centripetal migration drives spontaneous healing process after spinal cord injury

Kazu Kobayakawa1,2,3,4, Yasuyuki Ohkawa5, Shingo Yoshizaki1,2

  • 1Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.

Science Advances
|May 21, 2019
PubMed

Insights

Macrophages lacking IRF8 fail to migrate to spinal cord injury sites, worsening outcomes. Promoting IRF8-dependent migration improves recovery, revealing a therapeutic target for central nervous system injury.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Traumatic spinal cord injury (SCI) involves inflammatory cell infiltration, particularly macrophages, into lesion sites.
  • The precise role of macrophage spatiotemporal dynamics in SCI pathophysiology remains unclear.

Purpose of the Study:

  • To investigate the role of macrophage migration dynamics in SCI.
  • To elucidate the mechanisms underlying macrophage recruitment and their impact on SCI recovery.

Main Methods:

  • Utilized mouse models of SCI to study macrophage infiltration and migration patterns.
  • Employed time-lapse imaging and pharmacological interventions targeting IRF8 and purinergic receptors.
  • Assessed axonal loss, remyelination, and functional outcomes post-injury.

Main Results:

  • Macrophages migrate centripetally towards the SCI epicenter, guided by the C5a chemoattractant gradient.
  • Macrophages deficient in interferon regulatory factor 8 (IRF8) exhibit scattered distribution and impaired migration.
  • IRF8-dependent migration is mediated by purinergic receptors involved in C5a-directed movement.
  • Loss of IRF8-driven migration leads to increased axonal damage, reduced remyelination, and poor functional recovery.
  • Pharmacological enhancement of IRF8 activation promotes macrophage centripetal migration and improves SCI outcomes.

Conclusions:

  • Macrophage centripetal migration, regulated by IRF8, is crucial for limiting damage and promoting recovery after SCI.
  • Targeting IRF8-mediated macrophage migration presents a promising therapeutic strategy for central nervous system injuries.

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