title: IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses.
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.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Changchun
authors.initials: C
authors.lastname: Chen
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Itakura
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Nelson
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Ming
authors.initials: M
authors.lastname: Sheng
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Laurent
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Lorenz A
authors.initials: LA
authors.lastname: Fenk
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Butcher
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Ramanujan S
authors.initials: RS
authors.lastname: Hegde
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Mario
authors.initials: M
authors.lastname: de Bono
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D012677:Sensation / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000621115:ACTL-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D020381:Interleukin-17; C000621114:NFKI-1 protein, C elegans; D053722:Receptors, Interleukin-17; D010100:Oxygen