Age-dependent immune and lymphatic responses after spinal cord injury

• Published in: Neuron (Cambridge, Mass.) Mass.), 2023-07, Vol.111 (14), p.2155-2169.e9
• Main Authors: Salvador, Andrea Francesca M., Dykstra, Taitea, Rustenhoven, Justin, Gao, Wenqing, Blackburn, Susan M., Bhasiin, Kesshni, Dong, Michael Q., Guimarães, Rafaela Mano, Gonuguntla, Sriharsha, Smirnov, Igor, Kipnis, Jonathan, Herz, Jasmin
• Format: Article
• Language: English
• Subjects: Animals; Endothelial Cells - pathology; immune response to injury; lymphatics; macrophages; Mammals; meninges; Mice; microglia; Microglia - pathology; Myeloid Cells; neuroimmunology; Spinal Cord - pathology; Spinal Cord Injuries - pathology; spinal cord injury
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2023.04.011

Spinal cord injury (SCI) causes lifelong debilitating conditions. Previous works demonstrated the essential role of the immune system in recovery after SCI. Here, we explored the temporal changes of the response after SCI in young and aged mice in order to characterize multiple immune populations within the mammalian spinal cord. We revealed substantial infiltration of myeloid cells to the spinal cord in young animals, accompanied by changes in the activation state of microglia. In contrast, both processes were blunted in aged mice. Interestingly, we discovered the formation of meningeal lymphatic structures above the lesion site, and their role has not been examined after contusive injury. Our transcriptomic data predicted lymphangiogenic signaling between myeloid cells in the spinal cord and lymphatic endothelial cells (LECs) in the meninges after SCI. Together, our findings delineate how aging affects the immune response following SCI and highlight the participation of the spinal cord meninges in supporting vascular repair. [Display omitted] •scRNA-seq reveals age-related immune cell responses after SCI•Myeloid cell infiltration and diversification is impaired in aged mice after SCI•A subset of microglia in aged mice displays deficits at steady state and after SCI•Parenchymal and meningeal myeloid cells facilitate injury-related lymphangiogenesis Salvador et al. identify cellular and transcriptional age-dependent changes in infiltrating and resident immune cells of the spinal cord after contusive injury. They also reveal the formation of ectopic lymphangiogenesis in the spinal cord meninges upon injury, a process directed by myeloid cells.