Human-relevant near-organ neuromodulation of the immune system via the splenic nerve

Significance Bioelectronic modulation of the autonomic nervous system innervating the spleen represents a new therapeutic avenue. Studies in rodents suffer from the limitation that stimulation parameters and anatomy are not directly applicable to humans. This work demonstrates the translation of biological mechanisms in a large animal model with similar anatomical, histological, and functional characteristics for derivation of human-relevant parameters. Here, we show the scientific process for translating a bioelectronic medicine to clinical readiness. The results presented can be used in three ways: 1) as a system to demonstrate the species translation of neuroimmune modulation, 2) as an exemplar of how translational models can reveal additional potential mechanisms, and 3) as a general methodology to determine human-relevant stimulation parameters.