| First Author | Ouyang W | Year | 2013 |
| Journal | Immunity | Volume | 39 |
| Issue | 2 | Pages | 335-46 |
| PubMed ID | 23932572 | Mgi Jnum | J:208231 |
| Mgi Id | MGI:5562507 | Doi | 10.1016/j.immuni.2013.07.016 |
| Citation | Ouyang W, et al. (2013) TGF-beta cytokine signaling promotes CD8+ T cell development and low-affinity CD4+ T cell homeostasis by regulation of interleukin-7 receptor alpha expression. Immunity 39(2):335-46 |
| abstractText | Interleukin-7 receptor alpha chain (IL-7Ralpha) is induced upon T cell positive selection and controls thymic CD8-lineage specification and peripheral naive T cell homeostasis. How IL-7Ralpha expression is regulated in developing thymocytes is unclear. Here, we show that transforming growth factor beta (TGF-beta) signaling promoted IL-7Ralpha expression and CD8+ T cell differentiation. In addition, TGF-beta signaling was required for high IL-7Ralpha expression in CD4+ T cells bearing low-affinity T cell receptors, and the abrogation of TGF-beta receptor expression led to failed maintenance of peripheral CD4+ T cells. Compromised IL-7Ralpha expression in TGF-beta-receptor-deficient T cells was associated with increased expression of the Il7ra transcriptional repressor, Gfi-1. IL-7Ralpha transgenesis or T-cell-specific ablation of Gfi-1 restored IL-7Ralpha expression and largely ameliorated the development and homeostasis defects of TGF-beta-receptor-deficient T cells. These findings reveal functions for TGF-beta signaling in controlling IL-7Ralpha expression and in promoting T cell repertoire diversification. |
