The tango of immune and neural cells: orchestrating neuroinflammation mediated brain disorders.

The bidirectional interaction between immune cells and neural cells is the core effector unit of neuroinflammation, determining whether the central nervous system (CNS) maintains homeostasis or develops disease. Under physiological conditions, this interaction supports CNS homeostasis through microglial surveillance, astrocytic metabolic support (including the astrocyte-neuron lactate shuttle and glutamate reuptake), and blood-brain barrier (BBB) integrity. Under pathological states, dysregulated immune-neural crosstalk drives neuroinflammation. Damaged neurons activate microglia and astrocytes, which in turn secrete proinflammatory factors that impair neurons, reduce neurotrophic support, and disrupt BBB integrity. This interaction operates through cell surface receptor-ligand systems and soluble signals. Representative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), depression, and schizophrenia share common inflammatory features such as glial cell activation, BBB damage, and synaptic dysfunction, while exhibiting disease-specific pathological mechanisms. Clinical translation progress has been made in developing biomarkers for diagnosis, targeting immune cells and neural cells for therapy, and exploring emerging interventions like immunometabolic regulation and cell therapy. However, gaps remain in understanding cell type specificity, spatiotemporal dynamics, and achieving precise clinical application. Future interdisciplinary research will further advance the role of immune-neural interaction as a key target for preventing and treating neurological diseases, providing more precise diagnostic and therapeutic strategies.