The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity.
The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity.
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DOI：
10.1038/ni.3385
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发表时间：
2016-04
影响因子：
30.5
通讯作者：
Xiao C
中科院分区：
文献类型：
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作者：
Gonzalez-Martin A;Adams BD;Lai M;Shepherd J;Salvador-Bernaldez M;Salvador JM;Lu J;Nemazee D;Xiao C
自身反应性B细胞在多种自身免疫性疾病中发挥关键作用，但控制这些细胞的分子途径仍然知之甚少。我们对淋巴细胞表达的miRNA文库进行了体内功能筛选，并鉴定出microRNA miR-148a是B细胞耐受性的有效调节因子。升高的miR-148a表达通过抑制编码促凋亡因子Bim的Gadd45a、Pten和bcl2111的表达，促进未成熟B细胞在B细胞受体参与下的存活，从而损害B细胞的耐受性。此外，在狼疮患者和狼疮易感小鼠中经常出现的miR-148a表达增加，促进了狼疮小鼠模型中致死性自身免疫性疾病的发展。这些研究表明，miR-148a是B细胞耐受性和自身免疫的重要调节因子。
Autoreactive B cells play critical roles in a large diversity of autoimmune diseases, but the molecular pathways controlling these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed miRNA library and identified the microRNA miR-148a as a potent regulator of B cell tolerance. Elevated miR-148a expression impaired B cell tolerance by promoting the survival of immature B cells upon B cell receptor engagement via suppressing the expression of Gadd45a, Pten and Bcl2l11, which encodes the pro-apoptotic factor Bim. Furthermore, increased expression of miR-148a, which occurs frequently in lupus patients and lupus-prone mice, facilitated the development of lethal autoimmune disease in a lupus mouse model. These studies demonstrate that miR-148a functions as an important regulator of B cell tolerance and autoimmunity.
DOI：
10.1084/jem.164.1.156
发表时间：
1986-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Scott DW;Livnat D;Pennell CA;Keng P
通讯作者：
Keng P