Synergistic effect of TGF-β superfamily members on the induction of Foxp3+ Treg

Ling Lu, Jilin Ma, Xuehao Wang, Julie Wang, Feng Zhang, Jiangning Yu, Ge He, Bing Xu, David D. Brand, David A. Horwitz, Wei Shi, Song Guo Zheng

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Abstract

TGF-β plays an important role in the induction of Treg and maintenance of immunologic tolerance, but whether other members of TGF-β superfamily act together or independently to achieve this effect is poorly understood. Although others have reported that the bone morphogenetic proteins (BMP) and TGF-β 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-β to induce naïve CD4+CD25- cells to express Foxp3; however, BMP-2/4 and TGF-β 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-β. Data further advocate that TGF-β is a key signaling factor for Foxp3+ Treg development. In addition, the synergistic effect of BMP-2/4 and TGF-β indicates that the simultaneous manipulation of TGF-β and BMP signaling might have considerable effects in the clinical setting for the enhancement of Treg purity and yield.

Original languageEnglish (US)
Pages (from-to)142-152
Number of pages11
JournalEuropean Journal of Immunology
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2010

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Lu, L., Ma, J., Wang, X., Wang, J., Zhang, F., Yu, J., He, G., Xu, B., Brand, D. D., Horwitz, D. A., Shi, W., & Zheng, S. G. (2010). Synergistic effect of TGF-β superfamily members on the induction of Foxp3+ Treg. European Journal of Immunology, 40(1), 142-152. https://doi.org/10.1002/eji.200939618