The interleukin-4 enhancer CNS-2 is regulated by Notch signals and controls initial expression in NKT cells and memory-type CD4 T cells
The interleukin-4 enhancer CNS-2 is regulated by Notch signals and controls initial expression in NKT cells and memory-type CD4 T cells
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DOI：
10.1016/j.immuni.2006.04.009
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发表时间：
2006-06-01
期刊：
影响因子：
32.4
通讯作者：
Kubo, Masato
中科院分区：
文献类型：
--
作者：
Tanaka, Shinya;Tsukada, Jun;Kubo, Masato
辅助性T细胞(Th2)基因座染色质结构的表观遗传变化与Th2分化过程中IL-4和IL-13的表达密切相关。通过使用转基因绿色荧光蛋白(GFP)报告系统，我们发现位于114位点下游的保守非编码序列-2(CNS-2)是NKT细胞和CD44(Hi)记忆表型CD4(+)T细胞的结构性活性增强子。CD44(Hi)CD4(+)T细胞的CNS-2增强子活性和初始IL-4表达在CD4特异性缺失Notch信号转录物RBP-j的小鼠中被取消。体内激发后，CNS-2活性的CD4(+)T细胞的耗竭显著降低了Th2分化和抗原特异性IgE的产生。这些结果表明，Notch调控的CNS-2增强子控制NKT和记忆表型CD4(+)T细胞的初始IL-4表达，CNS-2激活的CD44(Hi)记忆表型T细胞在促进初始CD4(+)T细胞在过敏反应中的Th2分化中起重要作用。
Epigenetic changes in chromatin structure at the T helper (Th2) locus correlate with interukin-4 (IL-4) and IL-13 expression during Th2 differentiation. By using a transgenic green fluorescence protein (GFP) reporter system, we show that conserved noncoding sequence-2 (CNS-2), located downstream of the 114 locus, is a constitutively active enhancer in NKT cells as well as in a subset of CD44(hi) memory phenotype CD4(+) T cells. CNS-2 enhancer activity and initial IL-4 expression in CD44(hi) CD4(+) T cells were abolished in mice with a CD4-specific deletion of the transcriptional mediator of Notch signalling, Rbp-j. Depletion of CNS-2 active CD4(+) T cells markedly decreased Th2 differentiation from naive CD4(+) T cells and antigen-specific IgE production after in vivo priming. These findings indicate that Notch-regulated CNS-2 enhancer controls initial IL-4 expression In NKT and memory phenotype CD4(+) T cells and that CNS-2 active CD44(hi) memory phenotype T cells are important in facilitating Th2 differentiation of naive CD4(+) T cells in allergic responses.