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Synergistic effect of TGF‐β superfamily members on the induction of Foxp3 + Treg
Author(s) -
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
Publication year - 2010
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200939618
Subject(s) - smad , foxp3 , bmpr2 , bone morphogenetic protein , transforming growth factor , biology , microbiology and biotechnology , signal transduction , mapk/erk pathway , phosphorylation , il 2 receptor , transforming growth factor beta , immunology , r smad , immune system , stem cell , t cell , genetics , endoglin , gene , cd34
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.