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Dendritic cells control fibroblastic reticular network tension and lymph node expansion

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dc.contributor.authorActon, Sophie E.
dc.contributor.authorFarrugia, Aaron J.
dc.contributor.authorAstarita, Jillian L.
dc.contributor.authorMourão-Sá, Diego
dc.contributor.authorJenkins, Robert P.
dc.contributor.authorNye, Emma
dc.contributor.authorHooper, Steven
dc.contributor.authorvan Blijswijk, Janneke
dc.contributor.authorRogers, Neil C.
dc.contributor.authorSnelgrove, Kathryn J.
dc.contributor.authorRosewell, Ian
dc.contributor.authorMoita, Luis
dc.contributor.authorStamp, Gordon
dc.contributor.authorTurley, Shannon J.
dc.contributor.authorSahai, Erik
dc.contributor.authorReis e Sousa, Caetano
dc.date.accessioned2022-02-16T14:12:28Z
dc.date.available2022-02-16T14:12:28Z
dc.date.issued2014
dc.description© 2014 Macmillan Publishers Limited. All rights reservedpt_PT
dc.description.abstractAfter immunogenic challenge, infiltrating and dividing lymphocytes markedly increase lymph node cellularity, leading to organ expansion. Here we report that the physical elasticity of lymph nodes is maintained in part by podoplanin (PDPN) signalling in stromal fibroblastic reticular cells (FRCs) and its modulation by CLEC-2 expressed on dendritic cells. We show in mouse cells that PDPN induces actomyosin contractility in FRCs via activation of RhoA/C and downstream Rho-associated protein kinase (ROCK). Engagement by CLEC-2 causes PDPN clustering and rapidly uncouples PDPN from RhoA/C activation, relaxing the actomyosin cytoskeleton and permitting FRC stretching. Notably, administration of CLEC-2 protein to immunized mice augments lymph node expansion. In contrast, lymph node expansion is significantly constrained in mice selectively lacking CLEC-2 expression in dendritic cells. Thus, the same dendritic cells that initiate immunity by presenting antigens to T lymphocytes also initiate remodelling of lymph nodes by delivering CLEC-2 to FRCs. CLEC-2 modulation of PDPN signalling permits FRC network stretching and allows for the rapid lymph node expansion--driven by lymphocyte influx and proliferation--that is the critical hallmark of adaptive immunity.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNature. 2014 Oct 23;514(7523):498-502pt_PT
dc.identifier.doi10.1038/nature13814pt_PT
dc.identifier.eissn1476-4687
dc.identifier.issn0028-0836
dc.identifier.urihttp://hdl.handle.net/10451/51345
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNaturept_PT
dc.relation.publisherversionhttps://www.nature.com/pt_PT
dc.titleDendritic cells control fibroblastic reticular network tension and lymph node expansionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage502pt_PT
oaire.citation.issue7523pt_PT
oaire.citation.startPage498pt_PT
oaire.citation.titleNaturept_PT
oaire.citation.volume514pt_PT
person.familyNameMoita
person.givenNameLuis
person.identifier335918
person.identifier.ciencia-idCA1C-AE28-33FE
person.identifier.orcid0000-0003-0707-315X
person.identifier.ridL-1296-2013
person.identifier.scopus-author-id24554088300
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication600d2967-0c4d-4820-800e-bcbd58a21b60
relation.isAuthorOfPublication.latestForDiscovery600d2967-0c4d-4820-800e-bcbd58a21b60

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