CXCR4 signaling regulates repair Schwann cell infiltration into the spinal cord after spinal cord injury in mice

Abstract

Schwann cells are glial cells that myelinate neuronal axons in the peripheral nervous system (PNS). When the PNS is damaged, Schwann cells de-differentiate into p75-positive “repair Schwann cells,” which contribute to neural circuit regeneration. Interestingly, Schwann cells in the dorsal roots are known to be reprogrammed to repair Schwann cells even after spinal cord injury (SCI) and then migrate into the injured spinal cord. However, the molecular mechanism underlying the migration of repair Schwann cells remains unknown. Since a recent in vitro study revealed the importance of CXCR4 signaling in Schwann cell migration, we investigated whether CXCR4 signaling is involved in the PNS-to-central nervous system (CNS) migration of repair Schwann cells after SCI. We revealed that repair Schwann cells express CXCR4, and its ligand CXCL12 is upregulated in the injured spinal cord. We also found that the pharmacological inhibition of CXCR4 signaling decreased the infiltration of repair Schwann cells. Moreover, CXCR4 agonist administration effectively increased the infiltration of repair Schwann cells along with improved motor function. These findings strongly suggest the involvement of CXCR4 signaling in the PNS-to-CNS migration of repair Schwann cells after SCI.