Peripheral neuroimmune interactions: selected review and some clinical implications

Purpose: To provide a brief and focused review on peripheral neuroimmune interactions and their implications for some clinical disorders. Methods: Narrative review of the literature including of English-language articles published between 1985 and 2021 using PubMed and MEDLINE. Results: Many studies on experimental models and in vitro indicate that there are close interactions between the neural and immune systems. Processes from sensory afferents and autonomic efferents co-localize with immune cells and interact at discrete anatomical sites forming neuroimmune units. These neuroimmune interactions are bidirectional and mediated by a wide range of soluble factors including neuropeptides, classical neurotransmitters, cytokines, and other molecules that mediate complex cross-talk among nerves and immune cells. Small-diameter sensory afferents express a wide range of receptors that respond directly to tissue damage or pathogen signals and to chemokines, cytokines, or other molecules released from immune cells. Reciprocally, immune cells respond to neurotransmitters released from nociceptive and autonomic fibers. Neuroimmune interactions operate both at peripheral tissues and at the level of the central nervous system. Both centrally and peripherally, glial cells have a major active role in this bidirectional communication. Conclusions: Peripheral neuroimmune interactions are complex and importantly contribute to the pathophysiology of several disorders, including skin, respiratory, and intestinal inflammatory disorders typically associated with pain and altered barrier function. These interactions may be relevant for persistence of symptoms in disorders associated with intense immune activation.