Peripheral neurons: Master regulators of skin and mucosal immune response

Eur J Immunol. 2019 Nov;49(11):1984-1997. doi: 10.1002/eji.201848027. Epub 2019 Aug 7.


The body is innervated by a meshwork of heterogeneous peripheral neurons (including sensory neurons) which project virtually to all the organs. Peripheral neurons have been studied extensively in the context of their primary function of initiation of voluntary and involuntary movement, transmission of sensations and induction of appropriate behavioral response such as withdrawal to avoid tissue injury or scratching to remove irritating molecules. More recently, breakthrough articles have shown that, on top of their primary function of signal transmission to the spinal cord and brain, peripheral neurons (including afferent neurons) could directly sense environmental alarms and consequently regulate the development of various type of immune responses through the release of neuropeptides or growth factors. In this review, we discuss recent advances in the neural regulation of the immune response, both in physiological and pathological contexts by taking into account the type of organs (lungs, skin and gut), subtypes of peripheral neurons (sympathetic, nociceptive and intrinsic gut neurons) or immune cells and strains of pathogens studied. We also highlight future challenges in the field and potential therapeutic innovations targeting neuro-immune interactions.

Keywords: inflammation; neuro-immune interactions; neuropeptide; sensory neuron; tissue homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacterial Infections / immunology
  • Bacterial Infections / metabolism
  • Bacterial Infections / microbiology
  • Brain / immunology
  • Brain / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / metabolism
  • Humans
  • Immunity, Innate
  • Immunity, Mucosal*
  • Intercellular Signaling Peptides and Proteins / immunology
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lung / immunology
  • Lung / metabolism
  • Neuropeptides / immunology
  • Neuropeptides / metabolism
  • Nociception / physiology
  • Peripheral Nervous System / immunology*
  • Peripheral Nervous System / metabolism
  • Sensory Receptor Cells / immunology*
  • Sensory Receptor Cells / metabolism
  • Skin / immunology*
  • Skin / metabolism
  • Spinal Cord / immunology
  • Spinal Cord / metabolism
  • Synaptic Transmission / immunology*


  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Neuropeptides