The Nervous System and Immunity of the Skin

One might imagine that the central nervous system (CNS) could play an important role in the defence of the skin. The skin and the underlying dermis are densely innervated by afferent and efferent neurons. The CNS can detect and map a site of injury on the skin surface through its afferent circuits, and deliver a neutrally mediated response to that site through its efferent arms. Furthermore, once an injury is perceived by the CNS anywhere on the skin surface, the nervous system could activate defensive signals throughout the body, including uninjured skin in anticipation of potential downstream consequences of microbial spread from the site of injury. Finally, the nervous system can act within seconds, faster than a microbe can propagate. I believe the role played by the nervous system in the immunity of the skin can be appreciated through a careful analysis of two human diseases, infected ulcers on the feet of the diabetic, and erysipelas, superficial skin infection caused by Group A Streptococcus. In diabetes, the nervous system fails to protect the skin, while in erysipelas, the nervous system is being put on high alert. Here, I will tease out the role of the nervous system in the pathophysiology of each of these conditions, highlighting unappreciated immune functions of the nervous system, some of which are amenable to therapeutic intervention in these and other human diseases.