Article | Published:

IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses

Nature volume 542, pages 4348 (02 February 2017) | Download Citation

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.

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Acknowledgements

We thank the Caenorhabditis Genetics Center (funded by National Institutes of Health Infrastructure Program P40 OD010440) and the Japanese knockout consortium for strains, J. Hadfield and the Cambridge Research Institute Genomics Core for whole genome sequencing, Z. Soltesz for software, B. Gyenes for help screening for mutants, S. Flynn for help with mapping, and de Bono laboratory members for comments on the manuscript. This work was supported by a European Molecular Biology Organization Fellowship (to C.C.), a Japan Society for the Promotion of Science Post-doctoral Fellowship (to E.I.), the Medical Research Council, UK, and the European Research Council (Advanced Grant 269058) to M.d.B.

Author information

Author notes

    • Eisuke Itakura
    •  & Patrick Laurent

    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.).

Affiliations

  1. MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK

    • Changchun Chen
    • , Eisuke Itakura
    • , Geoffrey M. Nelson
    • , Ming Sheng
    • , Patrick Laurent
    • , Lorenz A. Fenk
    • , Ramanujan S. Hegde
    •  & Mario de Bono
  2. Department of Chemistry, University of Florida, Gainesville, Florida 32611, USA

    • Rebecca A. Butcher

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Contributions

C.C., E.I., R.S.H., and M.d.B. designed experiments. C.C., E.I., M.S., P.L., and L.A.F. performed experiments. G.N. did the genome sequence data analysis. R.A.B. provided reagents. C.C., E.I., R.S.H., and M.d.B. analysed the data. C.C. and M.d.B. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Mario de Bono.

Reviewer Information Nature thanks R. Garcia, O. Hobert and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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    Supplementary Information

    This file contains a Supplementary Figure and Supplementary Table 1. The Supplementary Figure shows the raw data for Figures 1c and 5 a, b, c, d and the Supplementary Table contains the strain list.

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https://doi.org/10.1038/nature20818

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