S100A9 Induces Macrophage M2 Polarization and Immunomodulatory Role in the Lesion Site After Spinal Cord Injury in Rats

Immune response is pivotal in the secondary injury of spinal cord injury (SCI). Polarization of macrophages (MΦ) influences the immune response in the secondary injury, which is regulated by several immune-related proteins. M2Φ plays the immunomodulatory role in the central nervous system. This study used bioinformatic analysis and machine algorithms to screen hub immune-related proteins after SCI and experimentally investigate the role of the target protein in the M2Φ polarization and immunomodulation in rats and in vitro after SCI. We downloaded GSE151371 and GSE45006, hub immune-related genes were screened using machine learning algorithms, and the expression of S100A9 was verified by datasets. Allen's weight-drop injury SCI model in Sprague-Dawley rat and bone marrow-derived rat MΦ with myelin debris model were used to study the effects of S100A9 on M2Φ polarization and immunomodulation at the lesion site and in vitro. Bioinformatic analysis showed that S100A9 acts as a hub immune-related gene in the SCI patients and rats. S100A9 increased at the lesion site in SCI rats, and its inhibition reduced CD206 and ARG-1 expression. Exogenous S100A9 promoted CD206 and ARG-1 expression in MΦ. S100A9 also increased the expression of PD-L1 and decreased MHC II at the lesion site in SCI rats and MΦ with myelin debris, and enhanced mitochondrial activity in rat MΦ with myelin debris. In conclusion, S100A9 is an indispensable factor in the immune process in secondary injury following SCI.