期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 40, 期 1, 页码 142-152出版社
WILEY
DOI: 10.1002/eji.200939618
关键词
Bone morphogenic proteins; Foxp3; Smad; TGF-beta; Treg
类别
资金
- NIH [R01 (HL068597)]
- National Natural Science Foundation of China [30728007]
- Medical Leading Talents of Jiangsu Province in China [2007-2-07]
- Zhejiang Province Natural Science Foundation of China [2090918]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL068597] Funding Source: NIH RePORTER
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.
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