Macrophage centripetal migration drives spontaneous healing process after spinal cord injury.

Abstract:

: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. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury.

journal_name

Sci Adv

journal_title

Science advances

authors

Kobayakawa K,Ohkawa Y,Yoshizaki S,Tamaru T,Saito T,Kijima K,Yokota K,Hara M,Kubota K,Matsumoto Y,Harimaya K,Ozato K,Masuda T,Tsuda M,Tamura T,Inoue K,Edgerton VR,Iwamoto Y,Nakashima Y,Okada S

doi

10.1126/sciadv.aav5086

subject

Has Abstract

pub_date

2019-05-15 00:00:00

pages

eaav5086

issue

5

issn

2375-2548

pii

aav5086

journal_volume

5

pub_type

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