Regulated Expression of miR-155 is Required for iNKT Cell Development.
Regulated Expression of miR-155 is Required for iNKT Cell Development.
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DOI：
10.3389/fimmu.2015.00140
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发表时间：
2015
影响因子：
7.3
通讯作者：
Colombo MP
中科院分区：
文献类型：
--
作者：
Burocchi A;Pittoni P;Tili E;Rigoni A;Costinean S;Croce CM;Colombo MP
不变的自然杀伤T细胞（iNKT细胞）是CD 1d限制的，具有免疫调节功能的脂质抗原反应性T淋巴细胞。iNKT细胞在胸腺中的发育经过后续阶段，由CD 44和NK1.1的表达定义，并由独特的基因表达程序（包括微小RNA）决定。在这里，我们研究了miR-155，一种参与大多数造血细胞分化的microRNA，是否在iNKT细胞发育中发挥任何作用。为此，我们评估了miR-155沿着iNKT细胞成熟在胸腺中的表达，并使用Lck-miR-155转基因小鼠研究了miR-155对iNKT细胞发育的影响，所述Lck-miR-155转基因小鼠在淋巴细胞特异性蛋白酪氨酸激酶（Lck）启动子下在T细胞谱系中过表达miR-155。我们发现miR-155在新选择的未成熟野生型iNKT细胞中表达，并沿着iNKT细胞分化而关闭。在转基因小鼠中，miR-155过表达导致第2阶段iNKT细胞成熟的实质性阻断，在胸腺中朝向外周iNKT细胞的总体减少，这与主流T细胞不同。此外，miR-155过表达对iNKT细胞分化的影响是细胞自主的。最后，我们确定Ets 1和ITK转录物为iNKT细胞分化中miR-155的相关靶点。总之，这些结果表明，严格控制miR-155表达是iNKT细胞发育所必需的。
Invariant natural killer T cells (iNKT cells) are CD1d-restricted, lipid antigen-reactive T lymphocytes with immunoregulatory functions. iNKT cell development in the thymus proceeds through subsequent stages, defined by the expression of CD44 and NK1.1, and is dictated by a unique gene expression program, including microRNAs. Here, we investigated whether miR-155, a microRNA involved in differentiation of most hematopoietic cells, played any role in iNKT cell development. To this end, we assessed the expression of miR-155 along iNKT cell maturation in the thymus, and studied the effects of miR-155 on iNKT cell development using Lck-miR-155 transgenic mice, which over express miR-155 in T cell lineage under the lymphocyte-specific protein tyrosine kinase (Lck) promoter. We show that miR-155 is expressed by newly selected immature wild-type iNKT cells and turned off along iNKT cells differentiation. In transgenic mice, miR-155 over-expression resulted in a substantial block of iNKT cell maturation at Stage 2, in the thymus toward an overall reduction of peripheral iNKT cells, unlike mainstream T cells. Furthermore, the effects of miR-155 over-expression on iNKT cell differentiation were cell autonomous. Finally, we identified Ets1 and ITK transcripts as relevant targets of miR-155 in iNKT cell differentiation. Altogether, these results demonstrate that a tight control of miR-155 expression is required for the development of iNKT cells.
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DOI：
10.1084/jem.20061692
发表时间：
2006-10-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cobb BS;Hertweck A;Smith J;O'Connor E;Graf D;Cook T;Smale ST;Sakaguchi S;Livesey FJ;Fisher AG;Merkenschlager M
通讯作者：
Merkenschlager M
影响因子：
50.3
作者：
Dadi, Saida;Le Noir, Sandrine;Asnafi, Vahid
通讯作者：
Asnafi, Vahid
影响因子：
4.4
作者：
Fedeli, Maya;Napolitano, Anna;Casorati, Giulia
通讯作者：
Casorati, Giulia
影响因子：
4.4
作者：
Felices, Martin;Berg, Leslie J.
通讯作者：
Berg, Leslie J.
DOI：
10.1073/pnas.0602266103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Costinean, S;Zanesi, N;Croce, CM
通讯作者：
Croce, CM