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

被引：93

作者：

Lu, Ling ^{[1
,2
]}

Ma, Jilin ^{[3
]}

Wang, Xuehao ^{[2
]}

Wang, Julie ^{[1
]}

Zhang, Feng ^{[2
]}

Yu, Jiangning ^{[3
]}

He, Ge ^{[3
]}

Xu, Bing ^{[4
]}

Brand, David D. ^{[5
]}

Horwitz, David A. ^{[1
]}

Shi, Wei ^{[4
]}

Zheng, Song Guo ^{[1
]}

机构：

[1] Univ So Calif, Keck Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90033 USA

[2] Nanjing Med Univ, Affiliated Hosp 1, Liver Transplantat Ctr,Minist Publ Hlth, Key Lab Living Donor Liver Transplantat, Nanjing, Peoples R China

[3] Zhejiang Tradit Chinese Med & Western Med Hosp, Div Rheumatol Immunol & Nephrol, Hangzhou, Zhejiang, Peoples R China

[4] Childrens Hosp Los Angeles, Dept Surg, Dev Biol Program, Los Angeles, CA 90027 USA

[5] Vet Affairs Med Ctr, Res Serv, Memphis, TN USA

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2010年 / 40卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Bone morphogenic proteins; Foxp3; Smad; TGF-beta; Treg; REGULATORY T-CELLS; GENERATED EX-VIVO; SUPPRESSOR FUNCTION; CONVERSION; IL-2; TRANSCRIPTION; PROMOTES; CD4(+); MAP;

D O I：

10.1002/eji.200939618

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：142 / 152

页数：11

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