Unraveling the Plastic Peripheral Neuroimmune Interactome

Sensory neurons and immune cells share a common microenvironmental niche for surveying tissue integrity. The immune and nervous systems both sense deviations in homeostasis and initiate protective responses and, upon malfunction, also jointly contribute to disease. Barrier tissues are heavily innervated by nociceptors, the sensory neurons that detect noxious stimuli, leading to pain and itch. The same tissues are also home to diverse immune cells that respond to infections and injury. The physical proximity of nociceptors and immune cells allows for direct local interactions between the two, independent of the CNS. We discuss in this study their ligand-receptor-based interactions and propose the need to shift from studying individual neuroimmune interactions to exploring the reciprocal neuroimmune interaction network in its entirety: the "neuroimmune interactome." Identification of the nature of the interactome in health and its plasticity in disease will unravel the functional consequences of interactions between nociceptors and immune cells.