Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2

Abstract

Tissue repair after spinal cord injury (SCI) requires mobilization of immune and glial cells to form a protective barrier that seals the wound and facilitates debris clearing, inflammatory containment, and matrix compaction. This process involves corralling, wherein phagocytic immune cells become confined to the necrotic core surrounded by an astrocytic border. Here, we elucidate a temporally distinct gene signature in injury-activated microglia/macrophages (IAM), which engages axon guidance pathways. Plexin-B2 is upregulated in IAM, which is required for motosensory recovery after SCI. Plexin-B2 deletion in myeloid cells impairs corralling, leading to diffuse tissue damage, inflammatory spillover, and hampered axon regeneration. Corralling begins early and requires Plexin-B2 in both microglia and macrophages. Mechanistically, Plexin-B2 promotes microglia motility, steers IAM away from colliding cells, and facilitates matrix compaction. Our data thus establish Plexin-B2 as an important link that integrates biochemical cues and physical interactions of IAM with the injury microenvironment during wound healing.

Data mining of human plasma proteins generates a multitude of highly predictive aging clocks that reflect different aspects of aging

“…For example, injecting B2M into young mice impairs neurogenesis and cognitive function (Smith et al, 2015) while treating aged mice with Timp2 enhances cognition and synaptic plasticity (Castellano et al, 2017). Ablating Cdon in satellite cells hinders muscle regeneration in mice (Bae et al, 2020), mice lacking Il6 exhibit impaired liver regeneration (Cressman et al, 1996), and the myeloid cell-specific ablation of Plxnb2 in mice impairs motor recovery following spinal cord injury (Zhou et al, 2020). Cardiac hypoplasia is caused by the deletion of tmem87b in zebrafish (Russell et al, 2014) while mice overexpressing Nab1 are resistant to cardiac hypertrophy (Buitrago et al, 2005).…”

Chronic Pain After Spinal Cord Injury: Is There a Role for Neuron-Immune Dysregulation?

“…Recent studies revealed that microglia are also important players in glial scar formation, by accumulating around the scar and modulating astrocyte proliferation during scar formation via insulin-like growth factor 1 (IGF-1) ( Bellver-Landete et al, 2019 ). Moreover, Zhou et al (2020) have also demonstrated that microglia form a concentric physical barrier between the center of the lesion and its border, promoting wound compaction and recovery.…”

Tripartite Motif Containing 52 Positively Regulates NF-κB Signaling by Promoting IκBα Ubiquitination in Lipopolysaccharide-Treated Microglial Cell Activation

“…Spinal cord injury (SCI) is a disastrous, life-altering occurrence, which is estimated by the World Health Organization to affect 250 000 to 500 000 individuals each year globally. Researchers are working on developing treatments for SCI, and microglial cells have become a promising area of research [ 1 – 4 ].…”