DEPTOR modulates activation responses in CD4⁺ T cells and enhances immunoregulation following transplantation.

ABSTRACT: 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 costimulator

SUBMITTER: Wedel J 

PROVIDER: S-EPMC6310634 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature