| First Author | Sun IH | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 2 | Pages | 481-492 |
| PubMed ID | 29884702 | Mgi Jnum | J:264075 |
| Mgi Id | MGI:6192166 | Doi | 10.4049/jimmunol.1701477 |
| Citation | Sun IH, et al. (2018) mTOR Complex 1 Signaling Regulates the Generation and Function of Central and Effector Foxp3(+) Regulatory T Cells. J Immunol 201(2):481-492 |
| abstractText | The mechanistic/mammalian target of rapamycin (mTOR) has emerged as a critical integrator of signals from the immune microenvironment capable of regulating T cell activation, differentiation, and function. The precise role of mTOR in the control of regulatory T cell (Treg) differentiation and function is complex. Pharmacologic inhibition and genetic deletion of mTOR promotes the generation of Tregs even under conditions that would normally promote generation of effector T cells. Alternatively, mTOR activity has been observed to be increased in Tregs, and the genetic deletion of the mTOR complex 1 (mTORC1)-scaffold protein Raptor inhibits Treg function. In this study, by employing both pharmacologic inhibitors and genetically altered T cells, we seek to clarify the role of mTOR in Tregs. Our studies demonstrate that inhibition of mTOR during T cell activation promotes the generation of long-lived central Tregs with a memory-like phenotype in mice. Metabolically, these central memory Tregs possess enhanced spare respiratory capacity, similar to CD8(+) memory cells. Alternatively, the generation of effector Tregs (eTregs) requires mTOR function. Indeed, genetic deletion of Rptor leads to the decreased expression of ICOS and PD-1 on the eTregs. Overall, our studies define a subset of mTORC1(hi) eTregs and mTORC1(lo) central Tregs. |
