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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Bone Morphogenetic Protein 4
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Bone Morphogenetic Protein Receptors
T-Lymphocytes
Thymocytes
Maintenance

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Lu, Ling ; Ma, Jilin ; Wang, Xuehao ; Wang, Julie ; Zhang, Feng ; Yu, Jiangning ; He, Ge ; Xu, Bing ; Brand, David D. ; Horwitz, David A. ; Shi, Wei ; Zheng, Song Guo. / Synergistic effect of TGF-β superfamily members on the induction of Foxp3 + Treg In: European Journal of Immunology. 2010 ; Vol. 40, No. 1. pp. 142-152.
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Lu, L, Ma, J, Wang, X, Wang, J, Zhang, F, Yu, J, He, G, Xu, B, Brand, DD, Horwitz, DA, Shi, W & Zheng, SG 2010, ' Synergistic effect of TGF-β superfamily members on the induction of Foxp3 + Treg ', European Journal of Immunology, vol. 40, no. 1, pp. 142-152. https://doi.org/10.1002/eji.200939618

Synergistic effect of TGF-β superfamily members on the induction of Foxp3 + Treg . / Lu, Ling; Ma, Jilin; Wang, Xuehao; Wang, Julie; Zhang, Feng; Yu, Jiangning; He, Ge; Xu, Bing; Brand, David D.; Horwitz, David A.; Shi, Wei; Zheng, Song Guo.

In: European Journal of Immunology, Vol. 40, No. 1, 01.01.2010, p. 142-152.

Research output: Contribution to journalArticle

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AU - Shi, Wei

AU - Zheng, Song Guo

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