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IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses
Open accessAbstract
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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“Previously described non-immune properties of IL-17 included (i) the regulation of social behavior in MIA models1,23, (ii) body temperature24,25, and (iii) neuromodulation in Caenorhabditis elegans2.”
From Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons (2020) · cites this paper as [24]
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Cites
The structure of the nervous system of the nematode Caenorhabditis elegans
White, J. G., Southgate, E., Thomson, J. N., & Brenner, S. (1986) · Philosophical Transactions of the Royal Society of London. B, Biological Sciences · doi:10.1098/rstb.1986.0056 · Cited by 5,589
Structure and signalling in the IL-17 receptor family
Gaffen, S. L. (2009) · Nature reviews. Immunology · doi:10.1038/nri2586 · Cited by 1,475
Functional Specialization of Interleukin-17 Family Members
Iwakura, Y., Ishigame, H., Saijo, S., & Nakae, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.012 · Cited by 1,289
The neural circuit for touch sensitivity in Caenorhabditis elegans
Chalfie, M., Sulston, J., White, J., Southgate, E., Thomson, J., & Brenner, S. (1985) · The Journal of Neuroscience · doi:10.1523/jneurosci.05-04-00956.1985 · Cited by 1,093
Nagai, T., Yamada, S., Tominaga, T., Ichikawa, M., & Miyawaki, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400417101 · Cited by 1,030
Neuromodulation of neuronal circuits: back to the future
Marder, E. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.010 · Cited by 904
de Bono, M., & Bargmann, C. I. (1998) · Cell · doi:10.1016/s0092-8674(00)81609-8 · Cited by 819
Neuromodulation of Brain States
Lee, S., & Dan, Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.012 · Cited by 697
Qian, Y., Liu, C., Hartupee, J., Altuntas, C. Z., Gulen, M. F., Jane-wit, D., Xiao, J., Lu, Y., Giltiay, N., Liu, J., et al. (2007) · Nature Immunology · doi:10.1038/ni1439 · Cited by 614
Microfluidics for in vivo imaging of neuronal and behavioral activity in Caenorhabditis elegans
Chronis, N., Zimmer, M., & Bargmann, C. I. (2007) · Nature Methods · doi:10.1038/nmeth1075 · Cited by 601
Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue
Gray, J. M., Karow, D. S., Lu, H., Chang, A. J., Chang, J. S., Ellis, R. E., Marletta, M. A., & Bargmann, C. I. (2004) · Nature · doi:10.1038/nature02714 · Cited by 591
Hymowitz, S. G., Filvaroff, E. H., Yin, J., Lee, J., Cai, L., Risser, P., Maruoka, M., Mao, W., Foster, J., Kelley, R. F., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.19.5332 · Cited by 548
Presynaptic facilitation by neuropeptide signaling mediates odor-driven food search
Root, C. M., Ko, K. I., Jafari, A., & Wang, J. W. (2011) · Cell · doi:10.1016/j.cell.2011.02.008 · Cited by 526
A hub-and-spoke circuit drives pheromone attraction and social behaviour in C. elegans
Macosko, E. Z., Pokala, N., Feinberg, E. H., Chalasani, S. H., Butcher, R. A., Clardy, J., & Bargmann, C. I. (2009) · Nature · doi:10.1038/nature07886 · Cited by 475
Self-citationA reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans
Pujol, N., Link, E. M., Liu, L. X., Kurz, C. L., Alloing, G., Tan, M., Ray, K. P., Solari, R. C. E., Johnson, C. D., & Ewbank, J. J. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00241-x · Cited by 450
Coordinated and compartmentalized neuromodulation shapes sensory processing in Drosophila
Cohn, R., Morantte, I., & Ruta, V. (2015) · Cell · doi:10.1016/j.cell.2015.11.019 · Cited by 430
Identification of a Targeting Factor for Posttranslational Membrane Protein Insertion into the ER
Stefanovic, S., & Hegde, R. S. (2007) · Cell · doi:10.1016/j.cell.2007.01.036 · Cited by 406
Self-citationRandom and targeted transgene insertion in Caenorhabditis elegans using a modified Mos1 transposon
Frøkjær‐Jensen, C., Davis, M. W., Sarov, M., Taylor, J. C., Flibotte, S., LaBella, M. L., Pozniakovsky, A., Moerman, D. G., & Jørgensen, E. M. (2014) · Nature Methods · doi:10.1038/nmeth.2889 · Cited by 357
Small-molecule pheromones that control dauer development in Caenorhabditis elegans
Butcher, R. A., Fujita, M., Schroeder, F. C., & Clardy, J. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.3 · Cited by 346
Self-citationExpression and regulation of an FMRFamide‐related neuropeptide gene family in Caenorhabditis elegans
Kim, K., & Li, C. (2004) · The Journal of Comparative Neurology · doi:10.1002/cne.20189 · Cited by 294
Genetic Analysis of Endocytosis in Caenorhabditis elegans: Coelomocyte Uptake Defective Mutants
Fares, H., & Greenwald, I. (2001) · Genetics · doi:10.1093/genetics/159.1.133 · Cited by 294
Recent advances in the IL-17 cytokine family
Gaffen, S. L. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.07.006 · Cited by 289
Social feeding in Caenorhabditis elegans is induced by neurons that detect aversive stimuli
de Bono, M., Tobin, D. M., Davis, M. W., Avery, L., & Bargmann, C. I. (2002) · Nature · doi:10.1038/nature01169 · Cited by 279
Yamazaki, S., Muta, T., & Takeshige, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103426200 · Cited by 277
The STIR-domain superfamily in signal transduction, development and immunity
Novatchkova, M., Leibbrandt, A., Werzowa, J., Neubüser, A., & Eisenhaber, F. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00067-7 · Cited by 255
Olfactory learning skews mushroom body output pathways to steer behavioral choice in Drosophila
Owald, D., & Waddell, S. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.10.002 · Cited by 251
Experience-Dependent Modulation of C. elegans Behavior by Ambient Oxygen
Cheung, B. H. H., Cohen, M., Rogers, C. M., Albayram, Ö., & de Bono, M. (2005) · Current Biology · doi:10.1016/j.cub.2005.04.017 · Cited by 216
Coates, J. C., & de Bono, M. (2002) · Nature · doi:10.1038/nature01170 · Cited by 198
Structural basis of receptor sharing by interleukin 17 cytokines
Ely, L. K., Fischer, S., & Garcia, K. C. (2009) · Nature Immunology · doi:10.1038/ni.1813 · Cited by 195
Behavioral avoidance of pathogenic bacteria by Caenorhabditis elegans
Meisel, J. D., & Kim, D. H. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.08.008 · Cited by 181
A Toolkit and Robust Pipeline for the Generation of Fosmid-Based Reporter Genes in C. elegans
Tursun, B., Cochella, L., Carrera, I., & Hobert, O. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004625 · Cited by 169
Butcher, R. A., Ragains, J. R., Kim, E., & Clardy, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806676105 · Cited by 156
Self-citationMAIL, a novel nuclear IκB protein that potentiates LPS‐induced IL‐6 production
Kitamura, H., Kanehira, K., Okita, K., Morimatsu, M., & Saito, M. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)02185-2 · Cited by 153
Karlsen, J. R., Borregaard, N., & Cowland, J. B. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.017129 · Cited by 146
Efficient genome editing in Caenorhabditis elegans by CRISPR-targeted homologous recombination
Chen, C., Fenk, L. A., & de Bono, M. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt805 · Cited by 141
Self-citationJang, H., Kim, K., Neal, S. J., Macosko, E. Z., Kim, D., Butcher, R. A., Zeiger, D. M., Bargmann, C. I., & Sengupta, P. (2012) · Neuron · doi:10.1016/j.neuron.2012.06.034 · Cited by 140
Self-citationNatural variation in a neural globin tunes oxygen sensing in wild Caenorhabditis elegans
Persson, A., Gross, E., Laurent, P., Busch, K. E., Bretes, H., & de Bono, M. (2009) · Nature · doi:10.1038/nature07820 · Cited by 136
Self-citationBehavioral Motifs and Neural Pathways Coordinating O2 Responses and Aggregation in C. elegans
Rogers, C. M., Persson, A., Cheung, B. H. H., & de Bono, M. (2006) · Current Biology · doi:10.1016/j.cub.2006.03.023 · Cited by 129
Tonic signaling from O2 sensors sets neural circuit activity and behavioral state
Busch, K. E., Laurent, P., Soltész, Z., Murphy, R. J., Faivre, O., Hedwig, B., Thomas, M. V., Smith, H., & de Bono, M. (2012) · Nature Neuroscience · doi:10.1038/nn.3061 · Cited by 118
Self-citationIsolation of a Novel Interleukin-1-inducible Nuclear Protein Bearing Ankyrin-repeat Motifs
Haruta, H., Kato, A., & Todokoro, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100075200 · Cited by 108
Decoding a neural circuit controlling global animal state in C. elegans
Laurent, P., Soltész, Z., Nelson, G. M., Chen, C., Arellano‐Carbajal, F., Levy, E. D., & de Bono, M. (2015) · eLife · doi:10.7554/elife.04241 · Cited by 81
Self-citationKao, C., Kim, C., Huang, F., & Wu, R. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708289200 · Cited by 80
Chen, C., Itakura, E., Weber, K. P., Hegde, R. S., & de Bono, M. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004082 · Cited by 58
Self-citationModulation of neural circuits: how stimulus context shapes innate behavior in Drosophila
Su, C.-Y., & Wang, J. W. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.04.008 · Cited by 48
Ryzhakov, G., Blazek, K. D., & Udalova, I. A. (2011) · Journal of Molecular Evolution · doi:10.1007/s00239-011-9450-7 · Cited by 22
Editorial overview: Neuromodulation: Tuning the properties of neurons, networks and behavior
McCormick, D. A., & Nusbaum, M. P. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.10.010 · Cited by 18
Flagged first, then by citations
Research works printed but not linked: 1
- Sulston, J. & Hodgkin, J. in The Nematode Caenorhabditis elegans (ed. Wood, W. B. ) 587–606 (Cold Spring Harbor Laboratory Press, 1988)
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Da Mesquita, S., Fu, Z., & Kipnis, J. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.022 · Cited by 479
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Alves de Lima, K., Rustenhoven, J., Da Mesquita, S., Wall, M., Salvador, A. F., Smirnov, I., Martelossi Cebinelli, G., Mamuladze, T., Baker, W., Papadopoulos, Z., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0776-4 · Cited by 416
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Salvador, A. F., de Lima, K. A., & Kipnis, J. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00508-z · Cited by 389
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Metadata
- 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
- Venue
- Nature
- Published
- 2017-01-18
- Volume
- 542
- Issue
- 7639
- Pages
- 43-48
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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