Bioelectrical and optogenetic modulation for neuroimmune therapeutics

Neuroimmune interactions are emerging as key regulators of inflammation, immunity, immune homeostasis, and disease progression. Neural circuits do not merely sense tissue injury, but also actively shape immune-cell recruitment, cytokine production, vascular function, and organ-level inflammatory outcomes. Here, we overview bioelectrical and optogenetic systems for neuroimmune modulation in diseases via the defined neural and inflammatory pathway. First, we review systemic neuroimmune modulating pathway and local neuroimmune modulators, and identify established neuroimmune molecular interactions in diseases. After that, we explain bioelectrical and optogenetic systems employed to modulate neuroimmune interactions. We evaluate representative studies with advanced delivery systems in consideration of neural target, immune effector, disease-relevant outcome, and safety. Finally, this review highlights both positive and negative clinical evidence of electroceuticals, and ultrasound-mediated and optogenetic systems predominantly in preclinical development. In summary and perspective, we prioritize and discuss the requirements for their further clinical translation. The integration of neural targeting with advanced materials and adaptive gene and drug delivery would be successfully harnessed for programmable therapies to modulate disease-relevant immune circuits without broadly suppressing host defense systems.