Cobb Bradley S, Hertweck Arnulf, Smith James, O'Connor Eric, Graf Daniel, Cook Terence, Smale Stephen T, Sakaguchi Shimon, Livesey Frederick J, Fisher Amanda G, Merkenschlager Matthias
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, England, UK.
J Exp Med. 2006 Oct 30;203(11):2519-27. doi: 10.1084/jem.20061692. Epub 2006 Oct 23.
Micro RNAs (miRNAs) regulate gene expression at the posttranscriptional level. Here we show that regulatory T (T reg) cells have a miRNA profile distinct from conventional CD4 T cells. A partial T reg cell-like miRNA profile is conferred by the enforced expression of Foxp3 and, surprisingly, by the activation of conventional CD4 T cells. Depleting miRNAs by eliminating Dicer, the RNAse III enzyme that generates functional miRNAs, reduces T reg cell numbers and results in immune pathology. Dicer facilitates, in a cell-autonomous fashion, the development of T reg cells in the thymus and the efficient induction of Foxp3 by transforming growth factor beta. These results suggest that T reg cell development involves Dicer-generated RNAs.
微小RNA（miRNA）在转录后水平调控基因表达。我们在此表明，调节性T（Treg）细胞具有与传统CD4 T细胞不同的miRNA谱。Foxp3的强制表达赋予了部分类似Treg细胞的miRNA谱，令人惊讶的是，传统CD4 T细胞的激活也能赋予此谱。通过消除Dicer（产生功能性miRNA的核糖核酸酶III酶）来消耗miRNA，会减少Treg细胞数量并导致免疫病理。Dicer以细胞自主方式促进胸腺中Treg细胞的发育以及转化生长因子β对Foxp3的有效诱导。这些结果表明，Treg细胞的发育涉及Dicer产生的RNA。
