| First Author | Gu AD | Year | 2015 |
| Journal | Immunity | Volume | 42 |
| Issue | 1 | Pages | 68-79 |
| PubMed ID | 25577439 | Mgi Jnum | J:254602 |
| Mgi Id | MGI:6112570 | Doi | 10.1016/j.immuni.2014.12.019 |
| Citation | Gu AD, et al. (2015) A critical role for transcription factor Smad4 in T cell function that is independent of transforming growth factor beta receptor signaling. Immunity 42(1):68-79 |
| abstractText | Transforming growth factor-beta (TGF-beta) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-beta signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-betaR) deletion and compromised T-cell-mediated tumor rejection. Although Smad4 was dispensable for T cell generation, homeostasis, and effector function, it was essential for T cell proliferation after activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-betaR-independent role for Smad4 in promoting T cell function, autoimmunity, and anti-tumor immunity. |
