dc.contributor.author | Lepletier, Ailin | |
dc.contributor.author | Hun, Michael L | |
dc.contributor.author | Hammett, Maree V | |
dc.contributor.author | Wong, Kahlia | |
dc.contributor.author | Naeem, Haroon | |
dc.contributor.author | Hedger, Mark | |
dc.contributor.author | Loveland, Kate | |
dc.contributor.author | Chidgey, Ann P | |
dc.date.accessioned | 2020-04-27T22:37:59Z | |
dc.date.available | 2020-04-27T22:37:59Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.doi | 10.1016/j.celrep.2019.05.045 | |
dc.identifier.uri | http://hdl.handle.net/10072/393432 | |
dc.description.abstract | A 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.relation.ispartofpagefrom | 3887 | |
dc.relation.ispartofpageto | 3901.e4 | |
dc.relation.ispartofissue | 13 | |
dc.relation.ispartofjournal | Cell Reports | |
dc.relation.ispartofvolume | 27 | |
dc.subject.fieldofresearch | Biochemistry and cell biology | |
dc.subject.fieldofresearch | Medical physiology | |
dc.subject.fieldofresearchcode | 3101 | |
dc.subject.fieldofresearchcode | 3208 | |
dc.subject.keywords | BMP4 | |
dc.subject.keywords | activin A | |
dc.subject.keywords | androgen blockade | |
dc.subject.keywords | follistatin | |
dc.subject.keywords | immune aging | |
dc.title | Interplay between Follistatin, Activin A, and BMP4 Signaling Regulates Postnatal Thymic Epithelial Progenitor Cell Differentiation during Aging | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Lepletier, 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.dateAccepted | 2019-05-14 | |
dcterms.license | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.date.updated | 2020-04-27T00:57:50Z | |
dc.description.version | Version 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.hasfulltext | Full Text | |
gro.griffith.author | Lepletier De Oliveira, Ailin | |