| First Author | Wertheimer T | Year | 2018 |
| Journal | Sci Immunol | Volume | 3 |
| Issue | 19 | PubMed ID | 29330161 |
| Mgi Jnum | J:364484 | Mgi Id | MGI:6851024 |
| Doi | 10.1126/sciimmunol.aal2736 | Citation | Wertheimer T, et al. (2018) Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration. Sci Immunol 3(19) |
| abstractText | The thymus is not only extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood, and this capacity diminishes considerably with age. We show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration via their production of bone morphogenetic protein 4 (BMP4) ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signaling or production by either pharmacologic or genetic inhibition impaired thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to increase their expression of Foxn1, a key transcription factor involved in TEC development, maintenance, and regeneration, and its downstream targets such as Dll4, a key mediator of thymocyte development and regeneration. These studies demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration and offer a potential clinical approach to enhance T cell immunity. |
