| First Author | Lepletier A | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 13 | Pages | 3887-3901.e4 |
| PubMed ID | 31242421 | Mgi Jnum | J:286165 |
| Mgi Id | MGI:6390096 | Doi | 10.1016/j.celrep.2019.05.045 |
| Citation | Lepletier A, et al. (2019) Interplay between Follistatin, Activin A, and BMP4 Signaling Regulates Postnatal Thymic Epithelial Progenitor Cell Differentiation during Aging. Cell Rep 27(13):3887-3901.e4 |
| abstractText | 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-1(lo) 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. |
