Central nervous system innate immune cells (CNS innate immune cells)

Central nervous system (CNS) innate immune cells, primarily consisting of microglia and border-associated macrophages, are the resident immune population responsible for maintaining neural homeostasis and responding to pathological insults (Prinz et al., 2019, Nature Reviews Immunology). Microglia act as the primary phagocytes of the brain, performing essential tasks such as synaptic pruning during development and the clearance of apoptotic cells and protein aggregates in the adult brain (Colonna & Butovsky, 2017, Nature Reviews Immunology). In the context of neurodegenerative diseases like Alzheimer's and Parkinson's, these cells can adopt a "disease-associated" phenotype characterized by the release of pro-inflammatory cytokines and a loss of homeostatic support, which exacerbates neuronal damage (Deczkowska et al., 2018, Cell). Therapeutic targeting of CNS innate immune cells involves modulating specific receptors, such as CSF1R to control cell density or TREM2 to enhance protective phagocytic activity (Butovsky & Weiner, 2018, Nature Reviews Neuroscience). While these cells represent a high-potential therapeutic frontier, challenges include ensuring brain penetrance of drugs and avoiding the disruption of the cells' vital physiological roles in the healthy brain.

Other names

MicrogliaCNS macrophagesResident myeloid cells of the CNSBorder-associated macrophagesBAMs

Inhibition of colony-stimulating factor 1 receptor (CSF1R) to deplete or modulate myeloid populations, agonism of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) to enhance phagocytosis, and modulation of Sphingosine-1-phosphate (S1P) receptors to alter cell trafficking and activation.