| First Author | Lu L | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 1 | Pages | 142-52 |
| PubMed ID | 19943263 | Mgi Jnum | J:155683 |
| Mgi Id | MGI:4415093 | Doi | 10.1002/eji.200939618 |
| Citation | Lu L, et al. (2010) Synergistic effect of TGF-beta superfamily members on the induction of Foxp3+ Treg. Eur J Immunol 40(1):142-52 |
| abstractText | TGF-beta plays an important role in the induction of Treg and maintenance of immunologic tolerance, but whether other members of TGF-beta superfamily act together or independently to achieve this effect is poorly understood. Although others have reported that the bone morphogenetic proteins (BMP) and TGF-beta have similar effects on the development of thymocytes and T cells, in this study, we report that members of the BMP family, BMP-2 and -4, are unable to induce non-regulatory T cells to become Foxp3+ Treg. Neutralization studies with Noggin have revealed that BMP-2/4 and the BMP receptor signaling pathway is not required for TGF-beta to induce naive CD4+CD25- cells to express Foxp3; however, BMP-2/4 and TGF-beta have a synergistic effect on the induction of Foxp3+ Treg. BMP-2/4 affects non-Smad signaling molecules including phosphorylated ERK and JNK, which could subsequently promote the differentiation of Foxp3+ Treg induced by TGF-beta. Data further advocate that TGF-beta is a key signaling factor for Foxp3+ Treg development. In addition, the synergistic effect of BMP-2/4 and TGF-beta indicates that the simultaneous manipulation of TGF-beta and BMP signaling might have considerable effects in the clinical setting for the enhancement of Treg purity and yield. |
