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Neuronal regulation of type 2 innate lymphoid cells via neuromedin U

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dc.contributor.authorCardoso, Vânia
dc.contributor.authorChesné, Julie
dc.contributor.authorRibeiro, Hélder
dc.contributor.authorGarcía Cassani, Bethania
dc.contributor.authorCarvalho, Tânia
dc.contributor.authorBouchery, Tiffany
dc.contributor.authorShah, Kathleen
dc.contributor.authorBarbosa-Morais, Nuno
dc.contributor.authorHarris, Nicola
dc.contributor.authorVeiga-Fernandes, Henrique
dc.date.accessioned2022-09-08T11:39:14Z
dc.date.available2022-09-08T11:39:14Z
dc.date.issued2017
dc.descriptionCopyright © 2017, Macmillan Publishers Limited, part of Springer Nature. All rights reserved.pt_PT
dc.description.abstractGroup 2 innate lymphoid cells (ILC2s) regulate inflammation, tissue repair and metabolic homeostasis, and are activated by host-derived cytokines and alarmins. Discrete subsets of immune cells integrate nervous system cues, but it remains unclear whether neuron-derived signals control ILC2s. Here we show that neuromedin U (NMU) in mice is a fast and potent regulator of type 2 innate immunity in the context of a functional neuron-ILC2 unit. We found that ILC2s selectively express neuromedin U receptor 1 (Nmur1), and mucosal neurons express NMU. Cell-autonomous activation of ILC2s with NMU resulted in immediate and strong NMUR1-dependent production of innate inflammatory and tissue repair cytokines. NMU controls ILC2s downstream of extracellular signal-regulated kinase and calcium-influx-dependent activation of both calcineurin and nuclear factor of activated T cells (NFAT). NMU treatment in vivo resulted in immediate protective type 2 responses. Accordingly, ILC2-autonomous ablation of Nmur1 led to impaired type 2 responses and poor control of worm infection. Notably, mucosal neurons were found adjacent to ILC2s, and these neurons directly sensed worm products and alarmins to induce NMU and to control innate type 2 cytokines. Our work reveals that neuron-ILC2 cell units confer immediate tissue protection through coordinated neuroimmune sensory responses.pt_PT
dc.description.sponsorshipV.C was supported by Fundação para a Ciência e Tecnologia (FCT), Portugal. J.C. by Fondation pour la Recherche Médicale (FRM), France, and by Marie Skłodowska-Curie fellowship (750030), EU; B.G.-C. by FP7 (289720), EU. N.L.B.-M. is supported by FCT, Portugal, and European Molecular Biology Organisation (EMBO). N.H. by Swiss National Science Foundation (310030_156517). H.V.-F. by ERC (647274), EU; Kenneth Rainin Foundation, USA; Crohn’s and Colitis Foundation of America, USA; and FCT, Portugal.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNature. 2017 Sep 14;549(7671):277-281pt_PT
dc.identifier.doi10.1038/nature23469pt_PT
dc.identifier.eissn1476-4687
dc.identifier.issn0028-0836
dc.identifier.urihttp://hdl.handle.net/10451/54373
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationStromal Cell- Immune Cell Interactions in Health and Disease
dc.relationGlia-derived factors in innate lymphoid cell sensing and intestinal defence
dc.relationImpact of Neuromedin U in type 2 immunity and mucosal defence
dc.relation.publisherversionhttps://www.nature.com/pt_PT
dc.titleNeuronal regulation of type 2 innate lymphoid cells via neuromedin Upt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleStromal Cell- Immune Cell Interactions in Health and Disease
oaire.awardTitleGlia-derived factors in innate lymphoid cell sensing and intestinal defence
oaire.awardTitleImpact of Neuromedin U in type 2 immunity and mucosal defence
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/289720/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/647274/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/750030/EU
oaire.citation.endPage281pt_PT
oaire.citation.issue7671pt_PT
oaire.citation.startPage277pt_PT
oaire.citation.titleNaturept_PT
oaire.citation.volume549pt_PT
oaire.fundingStreamFP7
oaire.fundingStreamH2020
oaire.fundingStreamH2020
person.familyNameChesné
person.familyNameRibeiro
person.familyNameGarcía Cassani
person.familyNameCarvalho
person.familyNameBARBOSA MORAIS
person.familyNameVeiga-Fernandes
person.givenNameJulie
person.givenNameHélder Manuel
person.givenNameBethania
person.givenNameTânia
person.givenNameNUNO LUÍS
person.givenNameHenrique
person.identifierI-2743-2013
person.identifier.ciencia-id4917-BD03-14F1
person.identifier.ciencia-id011F-EC42-7887
person.identifier.ciencia-id4C10-5743-02F8
person.identifier.ciencia-id5C19-CA77-A74D
person.identifier.ciencia-idC919-1B92-794F
person.identifier.orcid0000-0002-2330-7553
person.identifier.orcid0000-0001-8831-4386
person.identifier.orcid0000-0002-7090-9274
person.identifier.orcid0000-0002-1315-133X
person.identifier.orcid0000-0002-5283-5013
person.identifier.orcid0000-0002-1215-0538
person.identifier.orcid0000-0001-6216-1836
person.identifier.ridJ-3656-2013
person.identifier.scopus-author-id25653983600
person.identifier.scopus-author-id6507555084
person.identifier.scopus-author-id6508113770
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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