Eri1 regulates microRNA homeostasis and mouse lymphocyte development and antiviral function
Eri1 regulates microRNA homeostasis and mouse lymphocyte development and antiviral function
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DOI：
10.1182/blood-2011-11-394072
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发表时间：
2012-07-05
期刊：
影响因子：
20.3
通讯作者：
Ansel, K. Mark
中科院分区：
文献类型：
--
作者：
Thomas, Molly F.;Abdul-Wajid, Sarah;Ansel, K. Mark
自然杀伤(NK)细胞在宿主对感染和转化细胞的早期防御中起着关键作用。在这里，我们发现缺乏ERI1的小鼠在NK细胞的发育和成熟方面有细胞固有的缺陷。ERI1是一种保守的3‘到5’外核糖核酸酶，可以抑制RNA干扰。Eri1(-/-)NK细胞表现为骨髓(BM)Ly49受体获得延迟，外周Ly49D和Ly49H激活受体选择性减少。Eri1是小鼠巨细胞病毒(MCMV)免疫控制所必需的。在MCMV感染过程中，Eri1基因缺失的Ly49H(+)NK细胞不能有效地扩增，Eri1(-/-)T细胞对病毒的特异性反应也减弱。我们发现miRNAs是Eri1在小鼠淋巴细胞中的主要内源性小RNA靶标。缺失ERI1的NK和T细胞都表现出不依赖于序列的全局性miRNA丰度增加。异位表达Eri1挽救了成熟Eri1(-/-)T细胞中有缺陷的miRNA表达。因此，小鼠Eri1调节淋巴细胞中miRNA的动态平衡，是正常NK细胞发育和抗病毒免疫所必需的。(血。2012年；120(1)：130-142)
Natural killer (NK) cells play a critical role in early host defense to infected and transformed cells. Here, we show that mice deficient in Eri1, a conserved 3'-to-5' exoribonuclease that represses RNA interference, have a cell-intrinsic defect in NK-cell development and maturation. Eri1(-/-) NK cells displayed delayed acquisition of Ly49 receptors in the bone marrow (BM) and a selective reduction in Ly49D and Ly49H activating receptors in the periphery. Eri1 was required for immune-mediated control of mouse CMV ( MCMV) infection. Ly49H(+) NK cells deficient in Eri1 failed to expand efficiently during MCMV infection, and virus-specific responses were also diminished among Eri1(-/-) T cells. We identified miRNAs as the major endogenous small RNA target of Eri1 in mouse lymphocytes. Both NK and T cells deficient in Eri1 displayed a global, sequence-independent increase in miRNA abundance. Ectopic Eri1 expression rescued defective miRNA expression in mature Eri1(-/-) T cells. Thus, mouse Eri1 regulates miRNA homeostasis in lymphocytes and is required for normal NK-cell development and antiviral immunity. (Blood. 2012;120(1):130-142)