| First Author | Gu AD | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 3 | Pages | 905-10 |
| PubMed ID | 22219364 | Mgi Jnum | J:179925 |
| Mgi Id | MGI:5304623 | Doi | 10.1073/pnas.1108352109 |
| Citation | Gu AD, et al. (2012) Requirements of transcription factor Smad-dependent and -independent TGF-beta signaling to control discrete T-cell functions. Proc Natl Acad Sci U S A 109(3):905-10 |
| abstractText | TGF-beta modulates immune response by suppressing non-regulatory T (Treg) function and promoting Treg function. The question of whether TGF-beta achieves distinct effects on non-Treg and Treg cells through discrete signaling pathways remains outstanding. In this study, we investigated the requirements of Smad-dependent and -independent TGF-beta signaling for T-cell function. Smad2 and Smad3 double deficiency in T cells led to lethal inflammatory disorder in mice. Non-Treg cells were spontaneously activated and produced effector cytokines in vivo on deletion of both Smad2 and Smad3. In addition, TGF-beta failed to suppress T helper differentiation efficiently and to promote induced Treg generation of non-Treg cells lacking both Smad2 and Smad3, suggesting that Smad-dependent signaling is obligatory to mediate TGF-beta function in non-Treg cells. Unexpectedly, however, the development, homeostasis, and function of Treg cells remained intact in the absence of Smad2 and Smad3, suggesting that the Smad-independent pathway is important for Treg function. Indeed, Treg-specific deletion of TGF-beta-activated kinase 1 led to failed Treg homeostasis and lethal immune disorder in mice. Therefore, Smad-dependent and -independent TGF-beta signaling discretely controls non-Treg and Treg function to modulate immune tolerance and immune homeostasis. |
