| First Author | Park Y | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 12 | Pages | 5165-78 |
| PubMed ID | 24270422 | Mgi Jnum | J:207832 |
| Mgi Id | MGI:5559796 | Doi | 10.1172/JCI69751 |
| Citation | Park Y, et al. (2013) TSC1 regulates the balance between effector and regulatory T cells. J Clin Invest 123(12):5165-78 |
| abstractText | Mammalian target of rapamycin (mTOR) plays a crucial role in the control of T cell fate determination; however, the precise regulatory mechanism of the mTOR pathway is not fully understood. We found that T cell-specific deletion of the gene encoding tuberous sclerosis 1 (TSC1), an upstream negative regulator of mTOR, resulted in augmented Th1 and Th17 differentiation and led to severe intestinal inflammation in a colitis model. Conditional Tsc1 deletion in Tregs impaired their suppressive activity and expression of the Treg marker Foxp3 and resulted in increased IL-17 production under inflammatory conditions. A fate-mapping study revealed that Tsc1-null Tregs that lost Foxp3 expression gained a stronger effector-like phenotype compared with Tsc1-/- Foxp3+ Tregs. Elevated IL-17 production in Tsc1-/- Treg cells was reversed by in vivo knockdown of the mTOR target S6K1. Moreover, IL-17 production was enhanced by Treg-specific double deletion of Tsc1 and Foxo3a. Collectively, these studies suggest that TSC1 acts as an important checkpoint for maintaining immune homeostasis by regulating cell fate determination. |
