Notch regulates cytolytic effector function in CD8+ T cells.

Notch regulates cytolytic effector function in CD8+ T cells.
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DOI:
10.4049/jimmunol.0802598
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发表时间:
2009-03-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Osborne BA
Osborne BA
中科院分区:
其他
文献类型:
--
作者:
Cho OH;Shin HM;Miele L;Golde TE;Fauq A;Minter LM;Osborne BA

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幼稚CD8+ T细胞成熟为效应CTL是功能性适应性免疫系统的关键特征。CTL的发育部分取决于转录调节因子始中皮素(EOMES)的表达,其被认为调节两种关键效应分子穿孔素和颗粒酶B的表达。虽然EOMES是重要的效应CTL的发展,调节CD8+效应细胞成熟的精确机制仍然知之甚少。在这项研究中,我们表明,Notch1调节EOMES,穿孔素,和颗粒酶B的表达,通过直接结合到这些关键的效应分子的启动子。通过生物化学和遗传学上消除Notch信号传导,我们得出结论,Notch活性通过直接调节EOMES、穿孔素和颗粒酶B介导CTL活性。
The maturation of naive CD8+ T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8+ effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B.
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