IL-34 in neurological homeostasis and its multifaceted roles in central nervous system diseases.

Interleukin-34 (IL-34), a ligand for the macrophage colony-stimulating factor receptor (CSF1R), plays an indispensable role in the development and homeostasis maintenance of the central nervous system (CNS). This review systematically outlines the core mechanisms by which the IL-34/CSF1R signaling axis regulates the development, colonization, and functional differentiation of CNS-resident immune cells-including microglia and border-associated macrophages (BAMs). It highlights its role in critical physiological processes such as synaptic pruning, neural circuit maturation, and maintenance of blood-brain barrier integrity. Beyond its physiological functions, IL-34 modulates diverse neurological disorders-such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, ischemic stroke-with context dependent outcomes. It can confer neuroprotective effects but also drive disease progression under different conditions, providing new insights into CNS homeostasis balance and the complexity of pathological mechanisms.