RRC ID 53397
Author Chen C, Itakura E, Nelson GM, Sheng M, Laurent P, Fenk LA, Butcher RA, Hegde RS, de Bono M.
Title IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses.
Journal Nature
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.
Volume 542(7639)
Pages 43-48
Published 2017-2-2
DOI 10.1038/nature20818
PII nature20818
PMID 28099418
PMC PMC5503128
MeSH 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
IF 42.779
Times Cited 34
C.elegans tm5866 tm5124 tm5218 tm2167 tm5167