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 Advjournal_title
Science advancesauthors
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 Sdoi
10.1126/sciadv.aav5086subject
Has Abstractpub_date
2019-05-15 00:00:00pages
eaav5086issue
5issn
2375-2548pii
aav5086journal_volume
5pub_type
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