| First Author | Liu Y | Year | 2014 |
| Journal | Eur J Immunol | Volume | 44 |
| Issue | 2 | Pages | 521-32 |
| PubMed ID | 24165986 | Mgi Jnum | J:208913 |
| Mgi Id | MGI:5565388 | Doi | 10.1002/eji.201243291 |
| Citation | Liu Y, et al. (2014) AKT hyperactivation confers a Th1 phenotype in thymic Treg cells deficient in TGF-beta receptor II signaling. Eur J Immunol 44(2):521-32 |
| abstractText | The generation of CD4(+)Foxp3(+) Treg cells in the thymus is crucial for immune homeostasis and self-tolerance. Recent studies have shown Treg-cell plasticity when Th-related transcriptional factors and cytokines are present. However, the mechanisms that maintain the stability of Treg cells are poorly understood. Here, using mice with a T-cell-specific deletion of the transforming growth factor-beta receptor 2 (Tgfbr2(-)/(-) mice), we identify the restriction of AKT activation as a key event for the control of Treg-cell stability in Th1 inflammation. AKT regulation was evident in thymic CD4(+)Foxp3(+) Treg cells before they egressed to peripheral tissues. CD4(+)Foxp3(+) thymocytes from mice with the Tgfbr2 deletion expressed high levels of CXCR3 and T-bet, and produced IFN-gamma and TNF-alpha. Thymic Tgfbr2(-)/(-) Treg cells also showed an increase in the activation of AKT pathway. Enhanced AKT activity induced the expression of IFN-gamma both in natural and inducible Treg cells. Inhibition of AKT activity markedly attenuated the expression of IFN-gamma and TNF-alpha in thymic Tgfbr2(-)/(-) Treg cells in vivo. In addition, mixed bone marrow transplantation showed that TGF-beta signaling maintained Treg-cell stability in an intrinsic manner. Our results demonstrate that AKT hyperactivation contributes to the conversion of Treg cells to a Th1 phenotype. |
