| First Author | Lee S | Year | 2018 |
| Journal | EMBO Rep | Volume | 19 |
| Issue | 12 | PubMed ID | 30348891 |
| Mgi Jnum | J:318523 | Mgi Id | MGI:6859990 |
| Doi | 10.15252/embr.201845995 | Citation | Lee S, et al. (2018) Foxp3 expression in induced regulatory T cells is stabilized by C/EBP in inflammatory environments. EMBO Rep 19(12) |
| abstractText | Proper control of immune responses by Foxp3(+) regulatory T cells at inflamed sites is crucial for the prevention of immunopathology. TGF-beta-induced Foxp3(+) regulatory T (Treg) cells are generated in inflammatory environments as well as in steady-state conditions. Inflammatory cytokines such as IFN-gamma and IL-4 have an antagonistic effect on Treg cell conversion. However, it is not known how naive CD4(+) T cells overcome the inhibitory environment in inflamed sites to differentiate into Treg cells. Here, we show that CCAAT/enhancer-binding protein (C/EBP) functions as a safeguard that enhances Treg cell generation by dampening the inhibitory effect of IFN-gamma and IL-4 on Foxp3 expression. We find that C/EBPbeta is induced by retinoic acid and binds to the methyl-CRE sequence in the Foxp3 TSDR to sustain its expression. C/EBPbeta-transduced iTreg cells show more potent suppressive activity in mouse disease models. We also reveal that C/EBPbeta-transduced human iTreg cells exhibit more enhanced suppressor function. These results establish C/EBP as a new molecular target for enhancing the formation and stability of Treg cells in inflammatory environments. |
