miR-150 regulates the development of NK and iNKT cells.
miR-150 regulates the development of NK and iNKT cells.
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miR-150调节NK和Inkt细胞的发展。
DOI：
10.1084/jem.20111386
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发表时间：
2011-12-19
期刊：
影响因子：
--
通讯作者：
Lanier LL
中科院分区：
文献类型：
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作者：
Bezman NA;Chakraborty T;Bender T;Lanier LL
miR-150通过靶向转录因子c-Myb，促进NK细胞发育，干扰iNKT细胞发育。自然杀伤细胞（NK）和不变性NKT细胞（iNKT）在宿主防御病原体和启动适应性免疫反应中起着关键作用。mirna在NK和iNKT细胞的发育、成熟和功能中发挥重要作用，但具体mirna的作用尚不清楚。我们发现miR-150表达水平的调节对NK和iNKT细胞发育有不同的影响。靶向缺失miR-150的小鼠产生成熟NK细胞的能力受损，细胞谱系固有缺陷。相反，功能获得的miR-150转基因促进NK细胞的发育，NK细胞表现出更成熟的表型，对活化的反应更灵敏。相反，miR-150的过表达导致胸腺和外周淋巴器官中iNKT细胞的大量减少。转录因子c-Myb已被证明是miR-150的直接靶标。我们发现在Myb杂合骨髓嵌合体中NK细胞频率增加，iNKT细胞频率降低，这表明miR-150通过靶向c-Myb来不同地控制NK和iNKT细胞系的发育。
miR-150 promotes NK cell development and interferes with iNKT cell development due to the targeting the transcription factor c-Myb. Natural killer (NK) and invariant NK T (iNKT) cells are critical in host defense against pathogens and for the initiation of adaptive immune responses. miRNAs play important roles in NK and iNKT cell development, maturation, and function, but the roles of specific miRNAs are unclear. We show that modulation of miR-150 expression levels has a differential effect on NK and iNKT cell development. Mice with a targeted deletion of miR-150 have an impaired, cell lineage–intrinsic defect in their ability to generate mature NK cells. Conversely, a gain-of-function miR-150 transgene promotes the development of NK cells, which display a more mature phenotype and are more responsive to activation. In contrast, overexpression of miR-150 results in a substantial reduction of iNKT cells in the thymus and in the peripheral lymphoid organs. The transcription factor c-Myb has been shown to be a direct target of miR-150. Our finding of increased NK cell and decreased iNKT cell frequencies in Myb heterozygous bone marrow chimeras suggests that miR-150 differentially controls the development of NK and iNKT cell lineages by targeting c-Myb.