Dicer-Dependent MicroRNA Pathway Controls Invariant NKT Cell Development
Dicer-Dependent MicroRNA Pathway Controls Invariant NKT Cell Development
复制标题
DOI：
10.4049/jimmunol.0901361
复制
发表时间：
2009-08-15
影响因子：
4.4
通讯作者：
Casorati, Giulia
中科院分区：
文献类型：
--
作者：
Fedeli, Maya;Napolitano, Anna;Casorati, Giulia
不变NK T（iNKT）细胞是具有先天效应子功能的T淋巴细胞的单独谱系。它们表达对CD 1d呈递的脂质具有特异性的不变TCR，并且它们的发育和效应分化依赖于独特的基因表达程序。我们问这个程序是否包括microRNA，小的非编码RNA，转录后调节基因表达，并在细胞分化程序的控制中发挥关键作用。为此，我们研究了iNKT细胞在小鼠中的发育，其中Dicer，产生功能性microRNA的RNase III酶，在皮质胸腺细胞中被删除。我们发现Dicer缺失导致胸腺中iNKT细胞的大量减少及其从外周中的消失，这与主流T细胞不同。在没有Dicer的情况下，iNKT细胞不能完成其先天效应子分化，并且由于细胞死亡增加而显示出有缺陷的稳态。iNKT细胞的分化和稳态需要细胞自主方式的Dicer。此外，我们确定了一个特定的iNKT细胞的miRNA谱，它表现出激活/效应T淋巴细胞的功能，与iNKT细胞经历激动剂胸腺选择的想法一致。总之，这些结果定义了Dicer依赖性miRNA途径在iNKT细胞生理学中的关键作用。免疫学杂志，2009，183：2506-2512.
Invariant NK T (iNKT) cells are a separate lineage of T lymphocytes with innate effector functions. They express an invariant TCR specific for lipids presented by CD1d and their development and effector differentiation rely on a unique gene expression program. We asked whether this program includes microRNAs, small noncoding RNAs that regulate gene expression posttranscriptionally and play a key role in the control of cellular differentiation programs. To this aim, we investigated iNKT cell development in mice in which Dicer, the RNase III enzyme that generates functional microRNAs, is deleted in cortical thymocytes. We find that Dicer deletion results in a substantial reduction of iNKT cells in thymus and their disappearance from the periphery, unlike mainstream T cells. Without Dicer, iNKT cells do not complete their innate effector differentiation and display a defective homeostasis due to increased cell death. Differentiation and homeostasis of iNKT cells require Dicer in a cell-autonomous fashion. Furthermore, we identify a miRNA profile specific for iNKT cells, which exhibits features of activated/effector T lymphocytes, consistent with the idea that iNKT cells undergo agonist thymic selection. Together, these results define a critical role of the Dicer-dependent miRNA pathway in the physiology of iNKT cells. The Journal of Immunology, 2009, 183: 2506-2512.