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dc.contributor.authorIzquierdo-Fernandez, Helena María 
dc.contributor.authorBrandi, Paola 
dc.contributor.authorGomez, Manuel J 
dc.contributor.authorConde-Garrosa, Ruth 
dc.contributor.authorPriego, Elena 
dc.contributor.authorEnamorado, Michel 
dc.contributor.authorMartinez-Cano, Sarai 
dc.contributor.authorSanchez, Iris 
dc.contributor.authorConejero, Laura 
dc.contributor.authorJimenez-Carretero, Daniel 
dc.contributor.authorMartin-Puig, Silvia 
dc.contributor.authorGuilliams, Martin
dc.contributor.authorSancho, David 
dc.date.accessioned2018-10-26T07:59:27Z
dc.date.available2018-10-26T07:59:27Z
dc.date.issued2018
dc.identifierISI:000441581000008
dc.identifier.citationCell Rep. 2018; 24(7):1738-1746
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6539
dc.description.abstractThe rapid transit from hypoxia to normoxia in the lung that follows the first breath in newborn mice coincides with alveolar macrophage (AM) differentiation. However, whether sensing of oxygen affects AM maturation and function has not been previously explored. We have generated mice whose AMs show a deficient ability to sense oxygen after birth by deleting Vhl, a negative regulator of HIF transcription factors, in the CD11c compartment (CD11c Delta Vhl mice). VHL-deficient AMs show an immature-like phenotype and an impaired self-renewal capacity in vivo that persists upon culture ex vivo. VHL-deficient phenotype is intrinsic in AMs derived from monocyte precursors in mixed bone marrow chimeras. Moreover, unlike control Vhl(fl/fl), AMs from CD11c Delta Vhl mice do not reverse pulmonary alveolar proteinosis when transplanted into Csf2rb(-/)(-) mice, demonstrating that VHL contributes to AM-mediated surfactant clearance. Thus, our results suggest that optimal AM terminal differentiation, self-renewal, and homeostatic function requires their intact oxygen-sensing capacity.
dc.description.sponsorshipWe are grateful to the members of the David Sancho lab for discussions and critical reading of the manuscript. We are grateful to Andre's Hidalgo for providing DsRed mice, to Stefanie K. Wculek for helping with BM transplantation, and to Natalia Pietrosemoli for support in the in silico analysis. We thank the CNIC facilities and personnel for technical support and S. Bartlett for editorial assistance. H.M.I. was funded by the Spanish Ministerio de Ciencia, Innovacion y Universidades (MICINN; BES-2011-044928). Work in the David Sancho laboratory is funded by the CNIC and grant SAF2016-79040-R from MICINN, Agencia Estatal de Investigacion, and Fondo Europeo de Desarrollo Regional (FEDER); B2017/BMD-3733 Immunothercan-CM from Comunidad de Madrid; RD16/0015/0018-REEM from FIS-Instituto de Salud Carlos III, MICINN, and FEDER; Acteria Foundation; Constantes y Vitales prize (Atresmedia); La Marato de TV3 Foundation (201723); the European Commission (635122-PROCROP H2020); and the European Research Council (ERC-2016-Consolidator Grant 725091). The CNIC is supported by the MICINN and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).
dc.language.isoeng
dc.publisherCell Press
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectTISSUE-RESIDENT MACROPHAGES
dc.subjectCOLONY-STIMULATING FACTOR
dc.subjectGM-CSF
dc.subjectFETAL MONOCYTES
dc.subjectHYPOXIA
dc.subjectDEVELOP
dc.subjectLUNG
dc.subjectMICE
dc.subjectINFLAMMATION
dc.subjectHIF-1-ALPHA
dc.titleVon Hippel-Lindau Protein Is Required for Optimal Alveolar Macrophage Terminal Differentiation, Self-Renewal, and Function
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID30110631
dc.format.volume24
dc.format.page1738-1746
dc.identifier.doi10.1016/j.celrep.2018.07.034
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (ESPAÑA)
dc.contributor.funderAgencia Estatal de Investigación (España)
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderComunidad de Madrid
dc.contributor.funderInstituto de Salud Carlos III - ISCIII
dc.contributor.funderFondation Acteria
dc.contributor.funderAtresmedia Corporación de medios de comunicación
dc.contributor.funderFundacio la Marato
dc.contributor.funderEuropean Commission
dc.contributor.funderEuropean Research Council
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1016/j.celrep.2018.07.034
dc.identifier.journalCell Reports
dc.repisalud.orgCNICCNIC::Grupos de investigación::Inmunobiología
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/635122es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/725091es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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