IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses

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. Interleukin-17 functions as a neuromodulator in the roundworm Caenorhabditis elegans , acting directly on RMG hub interneurons to alter their response properties and contribution to behaviour. Interleukins can modulate sensory responses Molecular mediators of inflammation, such as interleukins, have been suggested to alter the nervous system, but any mechanisms have remained unclear. Now Mario de Bono and colleagues reveal that interleukin-17 (IL-17) functions as a neuromodulator in the roundworm Caenorhabditis elegans , acting in the RMG hub interneuron to increase the animal's escape and social aggregation response to oxygen. The work implicates further molecules of the conserved IL-17 pathways, and the expression of IL-17 in the vertebrate nervous system suggests that interleukins may also regulate behaviour in mammals.