Active research at the frontiers of immunology and neuroscience has identified multiple points of interaction and communication between the immune system and the nervous system. Immune cell activation stimulates neuronal circuits that regulate innate and adaptive immunity. Molecular mechanistic insights into the inflammatory reflex and other neuro-immune interactions have greatly advanced understanding immunity, and identified new therapeutic possibilities in inflammatory and autoimmune diseases. Recent successful clinical trials using bioelectronic devices that modulate the inflammatory reflex to significantly ameliorate rheumatoid arthritis and inflammatory bowel disease provide a path for using electrons as a therapeutic modality to target molecular mechanisms of immunity. Here we review mechanisms of peripheral sensory neuronal function modulation in response to immune challenges and neural regulation of immunity and inflammation and discuss the therapeutic implications of this mechanistic insight.

eTOC blurb
In this review Chavan, Pavlov and Tracey discuss mechanisms at the interface of the immune system and the nervous system as well as the role of neural pathways in the regulation of immunity. They also summarize the therapeutic implications of neuromodulation in animal models and clinical settings of inflammatory and autoimmune disease.

Mechanisms and Principles of Neuro-immune Communication
The Immune Impact on Afferent Neuronal Function
Efferent Neurocircuitry in the Regulation of Immunity
Reflexes in Neuro-immune Communication
Emerging Clinical Perspectives

Concluding remarks
Neuro-immune communication is an exciting area of research, bridging disciplines and addressing questions of great physiological importance and clinical relevance. We have described here mechanisms of this communication focusing on the functional role of sensory neurons in conditions of pathogen invasion, tissue injury and autoimmune derangements and the importance of efferent autonomic nerves in the regulation of inflammatory and autoimmune alterations. An integral part of the substantial progress in studying neuro-immune communication for the last 20 years has been the conceptual view that neuronal circuits organized in a reflexive manner regulate immunity. These neural circuits have an important protective role, but may be detrimental in case of massive homeostatic failure such as spinal cord injury. Molecular mechanisms at the interface between the neural and the immune component in these circuitries have been explored using pharmacological approaches and electrical neuromodulation for therapeutic benefit in numerous inflammatory conditions. This preclinical research has recently resulted in clinical studies exploiting neuromodulation in inflammatory and autoimmune diseases. Future research taking advantage of latest technologies for genetic molecular mapping, imaging and optogenetic and chemogenetic modulation will characterize in a greater detail the specificity of neuro-immune communication. These advances will contribute to the continuous progress in our basic understanding of neuroimmune regulatory mechanisms and will allow their precise targeting for therapeutic benefit.

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