Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptor

被引：120

作者：

Roncagalli, R

Taylor, JER

Zhang, SH

Shi, XC

Chen, RY

Cruz-Munoz, ME

Yin, L

Latour, S

Veillette, A

机构：

[1] Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada

[2] Univ Montreal, Program Mol Biol, Montreal, PQ H2W 1R7, Canada

[3] Int Agcy Res Canc, F-69372 Lyon, France

[4] Hop Necker Enfants Malad, INSERM, U429, F-75015 Paris, France

[5] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada

[6] McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada

来源：

NATURE IMMUNOLOGY | 2005年 / 6卷 / 10期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1038/ni1242

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

EAT-2 is an adaptor expressed in innate immune cells, including natural killer (NK) cells. It is closely related to the adaptor SAP, which regulates signaling lymphocyte activation molecule (SLAM)- related receptors by recruiting the kinase FynT to the receptors. Here we have studied the function of EAT-2 in NK cells by creating mice lacking or overexpressing EAT-2. Like SAP, EAT-2 was associated with the SLAM-related receptor 2B4 in NK cells. However, unlike SAP, EAT-2 was an inhibitor of NK cell function. EAT-2 repressed natural cytotoxicity and interferon-gamma secretion by a mechanism involving tyrosine phosphorylation of its C terminus. We have demonstrated a similar function for the adaptor ERT, a newly identified SAP family member expressed in mouse NK cells. These data identify a previously unknown mechanism of NK cell inhibition. Moreover, they indicate that EAT-2 and SAP have distinct and at times opposing functions in natural immunity.

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收藏

页码：1002 / 1010

页数：9

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