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dc.contributor.author | Izquierdo-Fernandez, Helena Maria | |
dc.contributor.author | Brandi, Paola | |
dc.contributor.author | Gomez, Manuel J | |
dc.contributor.author | Conde-Garrosa, Ruth | |
dc.contributor.author | Priego, Elena | |
dc.contributor.author | Enamorado, Michel | |
dc.contributor.author | Martinez-Cano, Sarai | |
dc.contributor.author | Sanchez, Iris | |
dc.contributor.author | Conejero, Laura | |
dc.contributor.author | Jimenez-Carretero, Daniel | |
dc.contributor.author | Martin-Puig, Silvia | |
dc.contributor.author | Guilliams, Martin | |
dc.contributor.author | Sancho, David | |
dc.date.accessioned | 2018-10-26T07:59:27Z | |
dc.date.available | 2018-10-26T07:59:27Z | |
dc.date.issued | 2018 | |
dc.identifier | ISI:000441581000008 | |
dc.identifier.citation | Cell Rep. 2018; 24(7):1738-1746 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6539 | |
dc.description.abstract | The 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.sponsorship | We 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.iso | eng | |
dc.publisher | Cell Press | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | TISSUE-RESIDENT MACROPHAGES | |
dc.subject | COLONY-STIMULATING FACTOR | |
dc.subject | GM-CSF | |
dc.subject | FETAL MONOCYTES | |
dc.subject | HYPOXIA | |
dc.subject | DEVELOP | |
dc.subject | LUNG | |
dc.subject | MICE | |
dc.subject | INFLAMMATION | |
dc.subject | HIF-1-ALPHA | |
dc.title | Von Hippel-Lindau Protein Is Required for Optimal Alveolar Macrophage Terminal Differentiation, Self-Renewal, and Function | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 30110631 | |
dc.format.volume | 24 | |
dc.format.page | 1738-1746 | |
dc.identifier.doi | 10.1016/j.celrep.2018.07.034 | |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | |
dc.contributor.funder | Agencia Estatal de Investigación (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Fondation ACTERIA (Acting on European Research in Immunology and Allergology) | |
dc.contributor.funder | Atresmedia | |
dc.contributor.funder | Fundación La Marató TV3 | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.1016/j.celrep.2018.07.034 | |
dc.identifier.journal | Cell Reports | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Inmunobiología | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/635122 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/725091 | es_ES |
dc.rights.accessRights | open access | es_ES |