| First Author | Kinsella S | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 1 | Pages | 109789 |
| PubMed ID | 34610317 | Mgi Jnum | J:334275 |
| Mgi Id | MGI:6883831 | Doi | 10.1016/j.celrep.2021.109789 |
| Citation | Kinsella S, et al. (2021) Attenuation of apoptotic cell detection triggers thymic regeneration after damage. Cell Rep 37(1):109789 |
| abstractText | The thymus, which is the primary site of T cell development, is particularly sensitive to insult but also has a remarkable capacity for repair. However, the mechanisms orchestrating regeneration are poorly understood, and delayed repair is common after cytoreductive therapies. Here, we demonstrate a trigger of thymic regeneration, centered on detecting the loss of dying thymocytes that are abundant during steady-state T cell development. Specifically, apoptotic thymocytes suppressed production of the regenerative factors IL-23 and BMP4 via TAM receptor signaling and activation of the Rho-GTPase Rac1, the intracellular pattern recognition receptor NOD2, and micro-RNA-29c. However, after damage, when profound thymocyte depletion occurs, this TAM-Rac1-NOD2-miR29c pathway is attenuated, increasing production of IL-23 and BMP4. Notably, pharmacological inhibition of Rac1-GTPase enhanced thymic function after acute damage. These findings identify a complex trigger of tissue regeneration and offer a regenerative strategy for restoring immune competence in patients whose thymic function has been compromised. |
