Niche-specific therapeutic targeting of myeloid cells in the central nervous system

Abstract

The central nervous system (CNS) can be subdivided into distinct anatomical and functional compartments, including the parenchyma, perivascular space, leptomeninges, and dura mater, etc. Each compartment hosts distinct immune cell populations, such as monocytes and diverse macrophages, which play critical roles in local tissue homeostasis and regional disease pathogenesis. Advances in single-cell technologies have revealed complex immune cell compositions and functions in these anatomical regions. This review summarizes the latest approaches for modulating myeloid cell subsets in a compartment-specific manner, including cellular strategies such as stem cell therapy, ex vivo gene treatment, bone marrow transplantation, as well as non-cellular strategies like antibodies, small molecules, and viral gene delivery to augment CNS immune responses and improve disease outcomes. We also discuss the challenges and requirements of translating targeting strategies from mice to humans.

Keywords: CNS-associated macrophages; leptomeninges; microglia; perivascular space.