Neuroimmune Modulation of Gut Function

Handb Exp Pharmacol. 2017;239:247-267. doi: 10.1007/164_2016_109.


Neuroimmune communications are facilitated by the production of neurotransmitters by immune cells and the generation of immune mediators by immune cells, which form a functional entity called the "neuroimmune synapse." There are several mechanisms that further facilitate neuroimmune interactions including the anatomic proximity between immune cells and nerves, the expression of receptors for neurotransmitters on immune cells and for immune mediators on nerves, and the receptor-mediated activation of intracellular signaling pathways that modulate nerve and immune phenotype and function. The bidirectional communication between nerves and immune cells is implicated in allostasis, a process that describes the continuous adaptation to an ever-changing environment. Neuroimmune interactions are amplified during inflammation by the influx of activated immune cells that significantly alter the microenvironment. In this context, the types of neurotransmitters released by activated neurons or immune cells can exert pro- or anti-inflammatory effects. Dysregulation of the enteric nervous system control of gastrointestinal functions, such as epithelial permeability and secretion as well as smooth muscle contractility, also contribute to the chronicity of inflammation. Persistent active inflammation in the gut leads to neuroimmune plasticity, which is a structural and functional remodeling in both the neural and immune systems. The importance of neuroimmune interactions has made them an emerging target in the development of novel therapies for GI pathologies.

Keywords: Innate lymphoid cell; Macrophage; Mast cell; Neuroimmune plasticity; Neuroimmune synapse; T cell; Vagal cholinergic reflex.

Publication types

  • Review

MeSH terms

  • Animals
  • Cellular Microenvironment
  • Enteric Nervous System / immunology*
  • Enteric Nervous System / physiopathology*
  • Gastrointestinal Diseases / immunology*
  • Gastrointestinal Diseases / physiopathology*
  • Gastrointestinal Diseases / therapy
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / innervation*
  • Humans
  • Immune System / immunology*
  • Immune System / physiopathology*
  • Immunity, Mucosal
  • Immunological Synapses
  • Inflammation / immunology
  • Inflammation / physiopathology
  • Macrophages / immunology
  • Mast Cells / immunology
  • Neuroglia / immunology
  • Neuroimmunomodulation*
  • Neuronal Plasticity
  • Reflex
  • T-Lymphocytes / immunology