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Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit

2021Journal article Restricted access
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dc.contributor.authorCardoso, Ana
dc.contributor.authorKlein Wolterink, Roel G. J.
dc.contributor.authorGodinho-Silva, Cristina
dc.contributor.authorDomingues, Rita G.
dc.contributor.authorRibeiro, Hélder
dc.contributor.authorda Silva, Joaquim Alves
dc.contributor.authorMahú, Inês
dc.contributor.authorDomingos, Ana I.
dc.contributor.authorVeiga Fernandes, Henrique
dc.date.accessioned2021-09-17T16:15:41Z
dc.date.available2021-09-17T16:15:41Z
dc.date.issued2021
dc.descriptionCopyright © 2021, The Author(s), under exclusive licence to Springer Nature Limitedpt_PT
dc.description.abstractSignals from sympathetic neurons and immune cells regulate adipocytes and thereby contribute to fat tissue biology. Interactions between the nervous and immune systems have recently emerged as important regulators of host defence and inflammation1-4. Nevertheless, it is unclear whether neuronal and immune cells co-operate in brain-body axes to orchestrate metabolism and obesity. Here we describe a neuro-mesenchymal unit that controls group 2 innate lymphoid cells (ILC2s), adipose tissue physiology, metabolism and obesity via a brain-adipose circuit. We found that sympathetic nerve terminals act on neighbouring adipose mesenchymal cells via the β2-adrenergic receptor to control the expression of glial-derived neurotrophic factor (GDNF) and the activity of ILC2s in gonadal fat. Accordingly, ILC2-autonomous manipulation of the GDNF receptor machinery led to alterations in ILC2 function, energy expenditure, insulin resistance and propensity to obesity. Retrograde tracing and chemical, surgical and chemogenetic manipulations identified a sympathetic aorticorenal circuit that modulates ILC2s in gonadal fat and connects to higher-order brain areas, including the paraventricular nucleus of the hypothalamus. Our results identify a neuro-mesenchymal unit that translates cues from long-range neuronal circuitry into adipose-resident ILC2 function, thereby shaping host metabolism and obesity.pt_PT
dc.description.sponsorshipWe thank Congento LISBOA-01-0145-FEDER-022170, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund). pAAV-Ef1a-mCherry-IRES-Cre was a gift from K. Deisseroth. PRV-614 (PRV-Bartha) was a gift from L. Enquist and E. Engel. F.C., C.G.-S., and R.G.D. were supported by Fundação para a Ciência e Tecnologia (FCT), Portugal. R.G.J.K.W. is supported by a Marie Skłodowska-Curie Individual fellowship (European Commission, 799810-TOPNIN), a Cancer Research Institute/Irvington Postdoctoral Fellowship and a Postdoctoral Junior Leader fellowship from la Caixa Foundation, ID100010434; LCF/BQ/PR20/11770004. H.V.-F. is supported by ERC (647274), EU, The Paul G. Allen Frontiers Group, US, and FCT, Portugal.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNature. 2021 Sep;597(7876):410-414pt_PT
dc.identifier.doi10.1038/s41586-021-03830-7pt_PT
dc.identifier.eissn1476-4687
dc.identifier.issn0028-0836
dc.identifier.urihttp://hdl.handle.net/10451/49544
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationLISBOA-01-0145-FEDER-022170pt_PT
dc.relation799810-TOPNINpt_PT
dc.relationGlia-derived factors in innate lymphoid cell sensing and intestinal defence
dc.relation.publisherversionhttps://www.nature.com/pt_PT
dc.titleNeuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuitpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleGlia-derived factors in innate lymphoid cell sensing and intestinal defence
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/647274/EU
oaire.citation.endPage414pt_PT
oaire.citation.issue7876pt_PT
oaire.citation.startPage410pt_PT
oaire.citation.titleNaturept_PT
oaire.citation.volume597pt_PT
oaire.fundingStreamH2020
person.familyNameCardoso
person.familyNameRibeiro
person.givenNameAna
person.givenNameHélder Manuel
person.identifier.ciencia-idC011-0637-E84F
person.identifier.ciencia-id011F-EC42-7887
person.identifier.orcid0000-0003-2618-5093
person.identifier.orcid0000-0002-7090-9274
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication3bf26703-7dfd-4acb-9e1a-a00dd570feb6
relation.isAuthorOfPublicationb499d016-1b68-4ecb-9d53-3ae71d54fec4
relation.isAuthorOfPublication.latestForDiscovery3bf26703-7dfd-4acb-9e1a-a00dd570feb6
relation.isProjectOfPublicationc24f9361-0173-4bae-a0e2-0c575ad55baa
relation.isProjectOfPublication.latestForDiscoveryc24f9361-0173-4bae-a0e2-0c575ad55baa

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