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dc.contributor.authorLepletier, Ailin
dc.contributor.authorHun, Michael L
dc.contributor.authorHammett, Maree V
dc.contributor.authorWong, Kahlia
dc.contributor.authorNaeem, Haroon
dc.contributor.authorHedger, Mark
dc.contributor.authorLoveland, Kate
dc.contributor.authorChidgey, Ann P
dc.date.accessioned2020-04-27T22:37:59Z
dc.date.available2020-04-27T22:37:59Z
dc.date.issued2019
dc.identifier.issn2211-1247
dc.identifier.doi10.1016/j.celrep.2019.05.045
dc.identifier.urihttp://hdl.handle.net/10072/393432
dc.description.abstractA key feature of immune functional impairment with age is the progressive involution of thymic tissue responsible for naive T cell production. In this study, we identify two major phases of thymic epithelial cell (TEC) loss during aging: a block in mature TEC differentiation from the pool of immature precursors, occurring at the onset of puberty, followed by impaired bipotent TEC progenitor differentiation and depletion of Sca-1lo cTEC and mTEC lineage-specific precursors. We reveal that an increase in follistatin production by aging TECs contributes to their own demise. TEC loss occurs primarily through the antagonism of activin A signaling, which we show is required for TEC maturation and acts in dissonance to BMP4, which promotes the maintenance of TEC progenitors. These results support a model in which an imbalance of activin A and BMP4 signaling underpins the degeneration of postnatal TEC maintenance during aging, and its reversal enables the transient replenishment of mature TECs.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom3887
dc.relation.ispartofpageto3901.e4
dc.relation.ispartofissue13
dc.relation.ispartofjournalCell Reports
dc.relation.ispartofvolume27
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchMedical Physiology
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode1116
dc.subject.keywordsBMP4
dc.subject.keywordsactivin A
dc.subject.keywordsandrogen blockade
dc.subject.keywordsfollistatin
dc.subject.keywordsimmune aging
dc.titleInterplay between Follistatin, Activin A, and BMP4 Signaling Regulates Postnatal Thymic Epithelial Progenitor Cell Differentiation during Aging
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationLepletier, A; Hun, ML; Hammett, MV; Wong, K; Naeem, H; Hedger, M; Loveland, K; Chidgey, AP, Interplay between Follistatin, Activin A, and BMP4 Signaling Regulates Postnatal Thymic Epithelial Progenitor Cell Differentiation during Aging, Cell Reports, 2019, 27 (13), pp. 3887-3901.e4
dcterms.dateAccepted2019-05-14
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated2020-04-27T00:57:50Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s) 2019. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND 4.0) License, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorLepletier de Oliveira, Ailin


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