Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets

The advent of neuroimmunology has dismantled the traditional doctrine of the brain's immune privilege, uncovering a sophisticated and dynamic bidirectional regulatory interplay between the nervous and immune systems. This review synthesizes pivotal advances in neuroimmunology, integrating recent anatomical and molecular discoveries to refine the understanding of neuro-immune communication. It highlights the pathological roles of neurotransmitters, cytokines, and their signaling networks in neurodegenerative, psychiatric, and neoplastic diseases, while critically examining contested regulatory mechanisms. The review further evaluates the clinical translational potential and challenges of innovative strategies such as vagus nerve stimulation, optogenetics, multiomics sequencing, and cytokine-targeted therapies. By integrating multidisciplinary perspectives, this review consolidates a theoretical framework for neuro-immune research and provides insights into precision medicine for related diseases. On the basis of synthesizing existing knowledge, it proposes promising research directions, identifies priorities and potential challenges for future investigations, and emphasizes the value of neuro-immune mechanisms in guiding therapeutic development-including target identification, design of individualized treatment strategies, and cross-disciplinary collaborative innovation to advance clinical interventions for neuro-immune diseases. Finally, the review delves into the recent advances and challenges in combined neuromodulation-immunotherapy strategies.