IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses

Nature. 2017 Feb 2;542(7639):43-48. doi: 10.1038/nature20818. Epub 2017 Jan 18.

Abstract

Interleukin-17 (IL-17) is a major pro-inflammatory cytokine: it mediates responses to pathogens or tissue damage, and drives autoimmune diseases. Little is known about its role in the nervous system. Here we show that IL-17 has neuromodulator-like properties in Caenorhabditis elegans. IL-17 can act directly on neurons to alter their response properties and contribution to behaviour. Using unbiased genetic screens, we delineate an IL-17 signalling pathway and show that it acts in the RMG hub interneurons. Disrupting IL-17 signalling reduces RMG responsiveness to input from oxygen sensors, and renders sustained escape from 21% oxygen transient and contingent on additional stimuli. Over-activating IL-17 receptors abnormally heightens responses to 21% oxygen in RMG neurons and whole animals. IL-17 deficiency can be bypassed by optogenetic stimulation of RMG. Inducing IL-17 expression in adults can rescue mutant defects within 6 h. These findings reveal a non-immunological role of IL-17 modulating circuit function and behaviour.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Interleukin-17 / metabolism*
  • Interneurons / drug effects
  • Interneurons / metabolism
  • Oxygen / metabolism
  • Oxygen / pharmacology
  • Receptors, Interleukin-17 / metabolism
  • Sensation / drug effects
  • Sensation / physiology*
  • Signal Transduction / drug effects

Substances

  • ACTL-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Interleukin-17
  • NFKI-1 protein, C elegans
  • Receptors, Interleukin-17
  • Oxygen