Astrocyte-microglia crosstalk via CSF1 and IFN-β promotes central nervous system repair

Despite accumulating evidence of functional interactions between astrocytes and microglia in central nervous system (CNS) injury and disease, mechanisms coordinating their response to CNS insults remain incompletely understood. We report that injury-reactive astrocytes at the lesion border upregulate colony-stimulating factor 1 (CSF1) required for microglial proliferation, wound closure, and motor recovery after focal spinal cord injury (SCI). Intriguingly, astrocyte-targeted deletion of CSF1 also reduces the cell number of border-forming astrocytes, revealing positive feedback regulation between astrocytes and microglia. We further show that microglia produce interferon β (IFN-β), which reciprocally supports astrocyte survival. Genetic disruption of interferon signaling in astrocytes in turn impairs astrocytic border formation, coordination with microglia in wound healing, and motor recovery. This work uncovers astrocyte-microglia crosstalk via CSF1 and IFN-β that synergizes the acute injury response of these cells for neural repair, providing insights into fundamental biology of astrocyte-microglia communication and its therapeutic potential.