| First Author | Wedel J | Year | 2019 |
| Journal | Am J Transplant | Volume | 19 |
| Issue | 1 | Pages | 77-88 |
| PubMed ID | 29969188 | Mgi Jnum | J:306489 |
| Mgi Id | MGI:6709544 | Doi | 10.1111/ajt.14995 |
| Citation | Wedel J, et al. (2019) DEPTOR modulates activation responses in CD4(+) T cells and enhances immunoregulation following transplantation. Am J Transplant 19(1):77-88 |
| abstractText | DEPTOR is an evolutionarily conserved cell-intrinsic binding partner of mTOR that functions as a negative regulator of signaling responses. In this study, we show that DEPTOR is expressed within CD4(+) T cells, and we observed that its relative level of expression modulates differentiation as well as glucose utilization within CD4(+) T effectors in vitro. Using knock-in mice, we also find that induced expression of DEPTOR within CD4(+) T regulatory cells stabilizes Foxp3 expression, shifts metabolism toward oxidative phosphorylation, and increases survival and suppressive function. In vivo, fully MHC mismatched cardiac allograft survival is significantly prolonged in knock-in recipients and sustained recipient expression of DEPTOR in combination with costimulatory blockade induces long-term graft survival. Furthermore, we show that the induced expression of DEPTOR in CD4(+) T effectors fails to inhibit acute allograft rejection. Rather, prolonged survival is dominantly mediated via induced expression and function of DEPTOR within recipient CD4(+) T regulatory cells. These collective findings identify DEPTOR as a novel protein that functions in CD4(+) T cells to augment immunoregulation in vitro and in vivo. |
