| First Author | Delgoffe GM | Year | 2009 |
| Journal | Immunity | Volume | 30 |
| Issue | 6 | Pages | 832-44 |
| PubMed ID | 19538929 | Mgi Jnum | J:150108 |
| Mgi Id | MGI:3849753 | Doi | 10.1016/j.immuni.2009.04.014 |
| Citation | Delgoffe GM, et al. (2009) The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 30(6):832-44 |
| abstractText | Effector T cell differentiation requires the simultaneous integration of multiple, and sometimes opposing, cytokine signals. We demonstrated mTOR's role in dictating the outcome of T cell fate. mTOR-deficient T cells displayed normal activation and IL-2 production upon initial stimulation. However, such cells failed to differentiate into T helper 1 (Th1), Th2, or Th17 effector cells. The inability to differentiate was associated with decreased STAT transcription factor activation and failure to upregulate lineage-specific transcription factors. Under normally activating conditions, T cells lacking mTOR differentiated into Foxp3(+) regulatory T cells. This was associated with hyperactive Smad3 activation in the absence of exogenous TGF-beta. Surprisingly, T cells selectively deficient in TORC1 do not divert to a regulatory T cell pathway, implicating both TORC1 and TORC2 in preventing the generation of regulatory T cells. Overall, our studies suggest that mTOR kinase signaling regulates decisions between effector and regulatory T cell lineage commitment. |
