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IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses

Author

Listed:
  • Changchun Chen

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue)

  • Eisuke Itakura

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue
    †Present addresses: Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Chiba, 263-8522, Japan (E.I.); Université Libre de Bruxelles, Laboratory of Neurophysiology, Campus Erasme, 808 Route de Lennik, 1070 Bruxelles, Belgium (P.L.).)

  • Geoffrey M. Nelson

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue)

  • Ming Sheng

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue)

  • Patrick Laurent

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue
    †Present addresses: Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Chiba, 263-8522, Japan (E.I.); Université Libre de Bruxelles, Laboratory of Neurophysiology, Campus Erasme, 808 Route de Lennik, 1070 Bruxelles, Belgium (P.L.).)

  • Lorenz A. Fenk

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue)

  • Rebecca A. Butcher

    (University of Florida)

  • Ramanujan S. Hegde

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue)

  • Mario de Bono

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue)

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.

Suggested Citation

  • Changchun Chen & Eisuke Itakura & Geoffrey M. Nelson & Ming Sheng & Patrick Laurent & Lorenz A. Fenk & Rebecca A. Butcher & Ramanujan S. Hegde & Mario de Bono, 2017. "IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses," Nature, Nature, vol. 542(7639), pages 43-48, February.
    • Handle: RePEc:nat:nature:v:542:y:2017:i:7639:d:10.1038_nature20818
    DOI: 10.1038/nature20818
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