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
|
Resource |
C.elegans |
tm5866
tm5124
tm5218
tm2167
tm5167 |