Interplay between Follistatin, Activin A, and BMP4 Signaling Regulates Postnatal Thymic Epithelial Progenitor Cell Differentiation during Aging

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Lepletier, Ailin
Hun, Michael L
Hammett, Maree V
Wong, Kahlia
Naeem, Haroon
Hedger, Mark
Loveland, Kate
Chidgey, Ann P
Griffith University Author(s)
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2019
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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.

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Cell Reports

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27

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13

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© 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.

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Biochemistry and cell biology

Medical physiology

BMP4

activin A

androgen blockade

follistatin

immune aging

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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

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