Regulation of B-cell development and tolerance by different members of the miR-17∼92 family microRNAs.
Regulation of B-cell development and tolerance by different members of the miR-17∼92 family microRNAs.
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DOI：
10.1038/ncomms12207
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发表时间：
2016-08-02
影响因子：
16.6
通讯作者：
Xiao C
中科院分区：
文献类型：
--
作者：
Lai M;Gonzalez-Martin A;Cooper AB;Oda H;Jin HY;Shepherd J;He L;Zhu J;Nemazee D;Xiao C
调节B细胞发育和耐受性的分子机制仍不完全清楚。在这项研究中，我们确定了miR-17 miR 92 microRNA簇在调节B细胞中枢耐受性中的关键作用，并证明这些miRNAs以细胞内在方式控制早期B细胞发育。虽然簇成员miR-19抑制Pten的表达并在调节B细胞耐受性中起关键作用，但miR-17通过其他分子途径控制早期B细胞发育。这些发现表明，单个microRNA簇的不同成员通过不同的分子途径对两个密切相关的B细胞发育阶段进行了差异控制。 microRNA簇17 - 92在B细胞分化中起关键作用。在这里，作者表明miR-19通过抑制PTEN的表达来调节B细胞耐受性，而miR- 17对于独立于Pten，Phlpp 2或Bim的早期B细胞发育是必需的。
The molecular mechanisms that regulate B-cell development and tolerance remain incompletely understood. In this study, we identify a critical role for the miR-17∼92 microRNA cluster in regulating B-cell central tolerance and demonstrate that these miRNAs control early B-cell development in a cell-intrinsic manner. While the cluster member miR-19 suppresses the expression of Pten and plays a key role in regulating B-cell tolerance, miR-17 controls early B-cell development through other molecular pathways. These findings demonstrate differential control of two closely linked B-cell developmental stages by different members of a single microRNA cluster through distinct molecular pathways. MicroRNA cluster 17∼92 plays a critical role in B-cell differentiation. Here the authors show that miR-19 regulates B-cell tolerance via suppressing the expression of PTEN, whereas miR- 17 is essential for early B-cell development independently of Pten, Phlpp2, or Bim.