| First Author | Delisle JS | Year | 2013 |
| Journal | Genes Immun | Volume | 14 |
| Issue | 2 | Pages | 115-26 |
| PubMed ID | 23328844 | Mgi Jnum | J:317952 |
| Mgi Id | MGI:6837199 | Doi | 10.1038/gene.2012.63 |
| Citation | Delisle JS, et al. (2013) The TGF-beta-Smad3 pathway inhibits CD28-dependent cell growth and proliferation of CD4 T cells. Genes Immun 14(2):115-26 |
| abstractText | Transforming growth factor-beta (TGF-beta) maintains self-tolerance through a constitutive inhibitory effect on T-cell reactivity. In most physiological situations, the tolerogenic effects of TGF-beta depend on the canonical signaling molecule Smad3. To characterize how TGF-beta/Smad3 signaling contributes to maintenance of T-cell tolerance, we characterized the transcriptional landscape downstream of TGF-beta/Smad3 signaling in resting or activated CD4 T cells. We report that in the presence of TGF-beta, Smad3 modulates the expression of >400 transcripts. Notably, we identified 40 transcripts whose expression showed Smad3 dependence in both resting and activated cells. This 'signature' confirmed the non-redundant role of Smad3 in TGF-beta biology and identified both known and putative immunoregulatory genes. Moreover, we provide genomic and functional evidence that the TGF-beta/Smad3 pathway regulates T-cell activation and metabolism. In particular, we show that TGF-beta/Smad3 signaling dampens the effect of CD28 stimulation on T-cell growth and proliferation. The impact of TGF-beta/Smad3 signals on T-cell activation was similar to that of the mTOR inhibitor Rapamycin. Considering the importance of co-stimulation on the outcome of T-cell activation, we propose that TGF-beta-Smad3 signaling may maintain T-cell tolerance by suppressing co-stimulation-dependent mobilization of anabolic pathways. |
