Optogenetic activation of local colonic sympathetic innervations attenuates colitis by limiting immune cell extravasation

Immunity. 2021 May 11;54(5):1022-1036.e8. doi: 10.1016/j.immuni.2021.04.007. Epub 2021 Apr 30.


The sympathetic nervous system is composed of an endocrine arm, regulating blood adrenaline and noradrenaline, and a local arm, a network of fibers innervating immune organs. Here, we investigated the impact of the local arm of the SNS in an inflammatory response in the colon. Intra-rectal insertion of an optogenetic probe in mice engineered to express channelrhodopsin-2 in tyrosine hydroxylase cells activated colonic sympathetic fibers. In contrast to systemic application of noradrenaline, local activation of sympathetic fibers attenuated experimental colitis and reduced immune cell abundance. Gene expression profiling showed decreased endothelial expression of the adhesion molecule MAdCAM-1 upon optogenetic stimulation; this decrease was sensitive to adrenergic blockers and 6-hydroxydopamine. Antibody blockade of MAdCAM-1 abrogated the optogenetic effect on immune cell extravasation into the colon and the pathology. Thus, sympathetic fibers control colonic inflammation by regulating immune cell extravasation from circulation, a mechanism likely relevant in multiple organs.

Keywords: MAdCAM-1; colitis; gut-brain axis; neuroimmunology; noradrenaline; optogenetics; sympathetic nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / immunology*
  • Colon / immunology*
  • Colon / innervation*
  • Intercellular Adhesion Molecule-1 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Optogenetics / methods
  • Organogenesis / immunology*
  • Sympathetic Nervous System / immunology*


  • Intercellular Adhesion Molecule-1