title: Regeneration-associated macrophages: a novel approach to boost intrinsic regenerative capacity for axon regeneration.
abstract: Axons in central nervous system (CNS) do not regenerate spontaneously after injuries such as stroke and traumatic spinal cord injury. Both intrinsic and extrinsic factors are responsible for the regeneration failure. Although intensive research efforts have been invested on extrinsic regeneration inhibitors, the extent to which glial inhibitors contribute to the regeneration failurein vivostill remains elusive. Recent experimental evidence has rekindled interests in intrinsic factors for the regulation of regeneration capacity in adult mammals. In this review, we propose that activating macrophages with pro-regenerative molecular signatures could be a novel approach for boosting intrinsic regenerative capacity of CNS neurons. Using a conditioning injury model in which regeneration of central branches of dorsal root ganglia sensory neurons is enhanced by a preceding injury to the peripheral branches, we have demonstrated that perineuronal macrophages surrounding dorsal root ganglia neurons are critically involved in the maintenance of enhanced regeneration capacity. Neuron-derived chemokine (C-C motif) ligand 2 (CCL2) seems to mediate neuron-macrophage interactions conveying injury signals to perineuronal macrophages taking on a soley pro-regenerative phenotype, which we designate as regeneration-associated macrophages (RAMs). Manipulation of the CCL2 signaling could boost regeneration potential mimicking the conditioning injury, suggesting that the chemokine-mediated RAM activation could be utilized as a regenerative therapeutic strategy for CNS injuries.
authors.affiliation: Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of Korea; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of Korea; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.
authors.forename: Hyuk Jun
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of Korea; Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.
authors.forename: Byung Gon
authors.identifier: 0000-0003-2233-9569
authors.initials: BG
authors.lastname: Kim
keywords: CCL2; M2 polarization; axon regeneration; cAMP; conditioning injury; neuron-macrophage interaction; regeneration-associated macrophage; spinal cord injury