T-bet concomitantly controls migration, survival, and effector functions during the development of Vα14i NKT cells
T-bet concomitantly controls migration, survival, and effector functions during the development of Vα14i NKT cells
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DOI：
10.1182/blood-2005-08-3103
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发表时间：
2006-04-01
期刊：
影响因子：
20.3
通讯作者：
Gapin, L
中科院分区：
文献类型：
--
作者：
Matsuda, JL;Zhang, QJ;Gapin, L
Vα14I自然杀伤T细胞(NKT)功能与多种疾病有关。驱动Vα14i NKT细胞发育的分子事件仍然难以捉摸。我们最近发现T-bet是这些细胞最终成熟所必需的。在这里，我们确定了T-bet在Vα14i NKT细胞谱系发育过程中的一些遗传靶点。对发育中的Vα14i NKT细胞进行了微阵列基因表达分析，为研究这些成熟事件提供了分子框架。在体外，T-bet在尚未表达T-bet的未成熟的Vα14i NKT细胞中异位表达，足以促进Vα14I NKT细胞的成熟，驱动多个基因的表达，包括那些参与迁移、存活和效应功能的基因。通过调节T辅助因子1(Th1)相关的细胞因子、趋化因子、趋化因子受体和参与细胞溶解的分子的表达，T-bet定义了成熟的Vα14i NKT细胞独特的谱系属性，并将这些属性与发育过程联系起来。
V alpha 14i natural killer T (NKT)-cell function has been implicated in a number of disease conditions. The molecular events that drive V alpha 14i NKT-cell development remain elusive. We recently showed that T-bet is required for the terminal maturation of these cells. Here we identify some of the genetic targets of T-bet during V alpha 14i NKT-cell lineage development. Microarray gene-expression analyses on developing V alpha 14i NKT cells were performed and provide a molecular framework to study these maturation events. In vitro ectopic expression of T-bet in immature V alpha 14i NKT cells, which do not yet express T-bet, was sufficient to promote V alpha 14i NKT-cell maturation, driving the expression of multiple genes, including those that participate in migration, survival, and effector functions. By regulating the expression of T-helper 1 (Th1)-associated cytokines, chemokines, chemokine receptors, and molecules involved in cytolysis, T-bet defines the unique lineage attributes of mature V alpha 14i NKT cells and acts to link these attributes to a developmental process.