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IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses

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Chen, Changchun, Itakura, Eisuke, Nelson, Geoffrey M., Sheng, Ming, Laurent, Patrick, Fenk, Lorenz A., Butcher, Rebecca A., Hegde, Ramanujan S., de Bono, Mario·2017·Nature

DOI 10.1038/nature20818PMC PMC5503128

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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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Authors: Chen, C., Itakura, E., Nelson, G. M., Sheng, M., Laurent, P., Fenk, L. A., Butcher, R. A., Hegde, R. S., & de Bono, M.
Affiliations: MRC Laboratory of Molecular Biology (GB)
University of Florida (US)
ORCID: Chen, Changchun
Itakura, Eisuke
Nelson, Geoffrey M.
Laurent, Patrick
Fenk, Lorenz A.
Butcher, Rebecca A.
Hegde, Ramanujan S.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2017-01-18
Volume: 542
Issue: 7639
Pages: 43-48
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature20818
PMC: PMC5503128
OpenAlex: W2576526246
Cited by: 127
References: 46
Citations by year: 2026: 8 · 2025: 16 · 2024: 12 · 2023: 16 · 2022: 11 · 2021: 11 · 2020: 17 · 2019: 12 · 2018: 13 · 2017: 11
FWCI: 7.10
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
Funders: National Institutes of Health (P40OD010440)
Japan Society for the Promotion of Science (16H06167, 16H01194)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: IL-17, neuromodulation, Caenorhabditis elegans, oxygen sensing, escape behavior, social aggregation, IL-17 signaling, optogenetic stimulation
MeSH terms: Animals, Behavior, Animal, Humans, Interneurons, Oxygen, Sensation, Signal Transduction, Caenorhabditis elegans, Interleukin-17, Caenorhabditis elegans Proteins, Receptors, Interleukin-17, HEK293 Cells

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IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses

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