Immune Cell-NSPC interactions: Friend or foe in CNS injury and repair?

Abstract

Neural stem/progenitor cells (NSPCs) play a crucial role in central nervous system (CNS) development, regeneration, and repair. However, their functionality and therapeutic potential are intricately modulated by interactions with immune cells, particularly macrophages and microglia. Microglia, as CNS-resident macrophages, are distinct from peripheral macrophages in their roles and characteristics, contributing to specialized functions within the CNS. Recent evidence suggests that microglia, as CNS-resident macrophages, contribute to the quality assurance of NSPCs by eliminating stressed or dysfunctional cells, yet the mechanisms underlying this process remain largely unexplored. Furthermore, macrophage polarization states, such as M1 and M2, appear to differentially influence NSPC quality, potentially impacting neurogenesis and regenerative outcomes. Identifying surface markers indicative of NSPC stress could provide a strategy for selecting optimal cells for transplantation therapies. Additionally, in vivo clonal labeling approaches may enable precise tracking of NSPC fate and their interactions with immune cells. Beyond macrophages and microglia, the roles of other immune cells, including T cells and neutrophils, particularly in injury and neurodegenerative disease contexts, in the context of CNS injury and disease are emerging areas of interest. Here, I discuss the emerging evidence supporting the interplay between the immune system and NSPCs, highlighting critical gaps in knowledge and proposing future research directions to harness immune-mediated mechanisms for optimizing neural regeneration and transplantation strategies.