Role of specialized sensory neuron subtypes in modulating peripheral immune responses

The immune and sensory nervous systems detect diverse threats, from tissue damage to infection, and coordinate protective responses to restore homeostasis. Like immune cells, sensory neurons exhibit remarkable heterogeneity, with advanced genetic models revealing that distinct subsets differentially regulate immune responses. Here, we review how various immune signals engage distinct subtypes of sensory neurons to mediate inflammatory pain, itch, relief, protective behavioral adaptations, and autonomic reflexes. We also highlight how specialized sensory neuron populations modulate immune function through the release of neuropeptides, neurokines, or glutamate. This functional specialization enables precise immunomodulation adapted to the kinetics and nature of immune responses, positioning sensory neurons as key regulators of host defense and tissue homeostasis.