Vagal neuroimmune circuits in inflammation and immunity.

The peripheral nervous system serves as a critical interface between the brain and the immune system, orchestrating bidirectional communication that maintains homeostasis and coordinates host defense responses. Peripheral neuroimmune crosstalk occurs through multiple anatomical pathways, including autonomic efferents, sympathetic circuits, and sensory afferents that detect tissue perturbation. Among these pathways, the vagus nerve has emerged as a prominent conduit for neuroimmune communication, integrating homeostatic and inflammatory cues to shape both local and systemic immune responses. In this review, we examine the structural and functional organization of vagal neuroimmune circuits, highlighting how vagal sensory neurons detect and encode inflammatory cues and how defined vagal pathways modulate immune responses in health and disease. We also discuss recent advances in bioelectronic medicine for treating chronic inflammatory disorders, emphasizing both therapeutic promise and current challenges that remain for clinical translation. Defining the cellular specificity and physiology of vagal neuroimmune circuits will be essential for developing precise neuromodulation strategies to treat inflammatory and autoimmune disorders.