Phospholipase Cγ1 is essential for T cell development, activation, and tolerance

被引：98

作者：

Fu, Guoping ^{[1
]}

Chen, Yuhong ^{[1
]}

Yu, Mei ^{[1
,2
]}

Podd, Andy ^{[1
,3
]}

Schuman, James ^{[1
,3
]}

He, Yinghong ^{[1
,2
]}

Di, Lie ^{[1
]}

Yassai, Maryam ^{[1
]}

Haribhai, Dipica ^{[4
]}

North, Paula E. ^{[5
]}

Gorski, Jack ^{[1
,3
]}

Williams, Calvin B. ^{[4
]}

Wang, Demin ^{[1
,3
]}

Wen, Renren ^{[1
]}

机构：

[1] Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI 53226 USA

[2] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 225001, Peoples R China

[3] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA

[4] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA

[5] Med Coll Wisconsin, Childrens Hosp Wisconsin, Dept Pathol & Lab Med, Milwaukee, WI 53226 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2010年 / 207卷 / 02期

基金：

美国国家卫生研究院;

关键词：

CBL-B; THYMOCYTE SELECTION; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; FOXP3; MUTATION; ADAPTER; DEPENDENCE; BCL10; NFAT;

D O I：

10.1084/jem.20090880

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Phospholipase C gamma 1 (PLC gamma 1) is an important signaling effector of T cell receptor (TCR). To investigate the role of PLC gamma 1 in T cell biology, we generated and examined mice with T cell-specific deletion of PLC gamma 1. We demonstrate that PLC gamma 1 deficiency affects positive and negative selection, significantly reduces single-positive thymocytes and peripheral T cells, and impairs TCR-induced proliferation and cytokine production, and the activation of ERK, JNK, AP-1, NFAT, and NF-kappa B. Importantly, PLC gamma 1 deficiency impairs the development and function of FoxP3(+) regulatory T cells, causing inflammatory/autoimmune symptoms. Therefore, PLC gamma 1 is essential for T cell development, activation, and tolerance.

引用

页码：309 / 318

页数：10

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