article published yes Changchun Chen author Eisuke Itakura author Geoffrey M. Nelson author Ming Sheng author Patrick Laurent author Lorenz A. Fenk author Rebecca A. Butcher author Ramanujan S. Hegde author Mario de Bono author 4E3FF80E-F248-11E8-B48F-1D18A9856A870000-0001-8347-0443 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. Springer Nature2017 eng 0028-0836 1476-4687 2809941810.1038/nature20818 542763943-48 yes C. Chen, E. Itakura, G.M. Nelson, M. Sheng, P. Laurent, L.A. Fenk, R.A. Butcher, R.S. Hegde, M. de Bono, Nature 542 (2017) 43–48. Chen C, Itakura E, Nelson GM, et al. IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses. <i>Nature</i>. 2017;542(7639):43-48. doi:<a href="https://doi.org/10.1038/nature20818">10.1038/nature20818</a> C. Chen <i>et al.</i>, “IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses,” <i>Nature</i>, vol. 542, no. 7639. Springer Nature, pp. 43–48, 2017. Chen, Changchun, Eisuke Itakura, Geoffrey M. Nelson, Ming Sheng, Patrick Laurent, Lorenz A. Fenk, Rebecca A. Butcher, Ramanujan S. Hegde, and Mario de Bono. “IL-17 Is a Neuromodulator of Caenorhabditis Elegans Sensory Responses.” <i>Nature</i>. Springer Nature, 2017. <a href="https://doi.org/10.1038/nature20818">https://doi.org/10.1038/nature20818</a>. Chen C, Itakura E, Nelson GM, Sheng M, Laurent P, Fenk LA, Butcher RA, Hegde RS, de Bono M. 2017. IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses. Nature. 542(7639), 43–48. Chen, Changchun, et al. “IL-17 Is a Neuromodulator of Caenorhabditis Elegans Sensory Responses.” <i>Nature</i>, vol. 542, no. 7639, Springer Nature, 2017, pp. 43–48, doi:<a href="https://doi.org/10.1038/nature20818">10.1038/nature20818</a>. Chen, C., Itakura, E., Nelson, G. M., Sheng, M., Laurent, P., Fenk, L. A., … de Bono, M. (2017). IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses. <i>Nature</i>. Springer Nature. <a href="https://doi.org/10.1038/nature20818">https://doi.org/10.1038/nature20818</a> 61172019-03-19T14:06:41Z2021-01-12T08:06:12Z