| First Author | Ouyang W | Year | 2010 |
| Journal | Immunity | Volume | 32 |
| Issue | 5 | Pages | 642-53 |
| PubMed ID | 20471291 | Mgi Jnum | J:160693 |
| Mgi Id | MGI:4454950 | Doi | 10.1016/j.immuni.2010.04.012 |
| Citation | Ouyang W, et al. (2010) Transforming growth factor-beta signaling curbs thymic negative selection promoting regulatory T cell development. Immunity 32(5):642-53 |
| abstractText | Thymus-derived naturally occurring regulatory T (nTreg) cells are necessary for immunological self-tolerance. nTreg cell development is instructed by the T cell receptor and can be induced by agonist antigens that trigger T cell-negative selection. How T cell deletion is regulated so that nTreg cells are generated is unclear. Here we showed that transforming growth factor-beta (TGF-beta) signaling protected nTreg cells and antigen-stimulated conventional T cells from apoptosis. Enhanced apoptosis of TGF-beta receptor-deficient nTreg cells was associated with high expression of proapoptotic proteins Bim, Bax, and Bak and low expression of the antiapoptotic protein Bcl-2. Ablation of Bim in mice corrected the Treg cell development and homeostasis defects. Our results suggest that nTreg cell commitment is independent of TGF-beta signaling. Instead, TGF-beta promotes nTreg cell survival by antagonizing T cell negative selection. These findings reveal a critical function for TGF-beta in control of autoreactive T cell fates with important implications for understanding T cell self-tolerance mechanisms. |
