H2-Ab1 deficiency in macrophages ameliorates spinal cord injury by regulating phagocytosis processing

Abstract Recently, an increasing number of studies have highlighted the pivotal role of phagocytosis of macrophages/microglia following spinal cord injury, positioning it as a promising therapeutic target. The H2-Ab1 gene encodes a part of the Major Histocompatibility Complex (MHC) Class II molecule, which is associated with cell activation and neuroinflammation. However, the specific functions and underlying mechanisms of H2-Ab1 in spinal cord injury remain to be fully understood. Here, we utilized lineage tracing and found that the cellular localization of MHC Class II was predominantly expressed on infiltrating macrophages. Next, we employed macrophage/microglia conditional knockout mice to investigate the to investigate the role and potential mechanisms of MHC Class II in spinal cord injury. The results indicated that the deletion of H2-Ab 1 in macrophages rather than microglia could improve the pathology following spinal cord injury. Furthermore, we demonstrated that H2-Ab1 promotes the formation of foamy macrophages and drives their polarization toward the M1 phenotype. This process leads to increased secretion of inflammatory cytokines, which in turn induces the accumulation of reactive oxygen species (ROS) and enhanced neuronal apoptosis. More importantly, these findings may offer a promising clinical translation strategy based on the modulation of H2-Ab1.