Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo.

Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo.
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NFIL3/E4BP4是在体内开发和成熟所必需的。

DOI:
10.1084/jem.20092176
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发表时间:
2009-12-21
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Mak TW
Mak TW
中科院分区:
其他
文献类型:
--
作者:
Kamizono S;Duncan GS;Seidel MG;Morimoto A;Hamada K;Grosveld G;Akashi K;Lind EF;Haight JP;Ohashi PS;Look AT;Mak TW

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核因子白细胞介素-3(Nfil 3;也称为E4结合蛋白4)是一种碱性区域亮氨酸拉链转录因子,在生长因子撤除条件下具有体外抗凋亡活性。为了研究Nfil 3在体内的作用,我们产生了基因靶向的Nfil 3缺陷(Nfil 3 −/−)小鼠。Nfil 3 −/−小鼠以正常孟德尔频率出生,并且大体上正常且可生育。尽管Nfil 3 −/−小鼠的T细胞、B细胞和自然杀伤(NK)T细胞数量正常,但NK细胞发育的特定中断导致外周成熟NK细胞数量严重减少。这种缺陷本质上是NK细胞固有的,导致在体内不能排斥MHC I类缺陷细胞,并在体外降低干扰素γ的产生和细胞溶解活性。我们的结果证实了Nfil 3对NK谱系细胞发育的特异性和基本要求。
Nuclear factor interleukin-3 (Nfil3; also known as E4-binding protein 4) is a basic region leucine zipper transcription factor that has antiapoptotic activity in vitro under conditions of growth factor withdrawal. To study the role of Nfil3 in vivo, we generated gene-targeted Nfil3-deficient (Nfil3−/−) mice. Nfil3−/− mice were born at normal Mendelian frequency and were grossly normal and fertile. Although numbers of T cells, B cells, and natural killer (NK) T cells were normal in Nfil3−/− mice, a specific disruption in NK cell development resulted in severely reduced numbers of mature NK cells in the periphery. This defect was NK cell intrinsic in nature, leading to a failure to reject MHC class I–deficient cells in vivo and reductions in both interferon γ production and cytolytic activity in vitro. Our results confirm the specific and essential requirement of Nfil3 for the development of cells of the NK lineage.
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