Role of TCR-induced extracellular signal-regulated kinase activation in the regulation of early IL-4 expression in naive CD4+ T cells
Role of TCR-induced extracellular signal-regulated kinase activation in the regulation of early IL-4 expression in naive CD4+ T cells
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DOI：
10.4049/jimmunol.170.5.2427
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发表时间：
2003-03-01
影响因子：
4.4
通讯作者：
Bottomly, K
中科院分区：
文献类型：
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作者：
Jorritsma, PJ;Brogdon, JL;Bottomly, K
虽然细胞外信号调节激酶（Erk）的激活影响IL-4的生产在各种实验系统中，其在Th分化的作用还不清楚。在这项研究中，我们发现Erk在TCR诱导的幼稚CD 4（+）T细胞Th分化过程中的IL-4表达中起关键作用。用高亲和力肽刺激CD 4（+）T细胞导致持续的Erk活化和Th 1分化。然而，Erk活性的降低导致IL-4产生和Th 2产生的急剧增加。CD 4（+）T细胞的RNA和核蛋白的分析48刺激后显示这是由于早期IL-4表达。有趣的是，短暂的Erk激活导致AP-1 DNA结合活性的改变和AP-1复合物的诱导，该复合物不含Fos蛋白，由Jun-Jun二聚体组成。这些数据表明，在存在强TCR信号的情况下，可以通过改变Erk活化的强度来诱导幼稚CD 4（+）T细胞中的IL-4表达。此外，这些数据表明，TCR诱导的Erk激活参与IL-4表达的调节，通过改变AP-1复合物的组成及其随后的DNA结合活性。
Although extracellular signal-regulated kinase (Erk) activation influences IL-4 production in various experimental systems, its role during Th differentiation is unclear. In this study, we show that Erk plays a critical role in IL-4 expression during TCR-induced Th differentiation of naive CD4(+) T cells. Stimulation of CD4(+) T cells with a high affinity peptide resulted in sustained Erk activation and Th1 differentiation. However, reduction of Erk activity led to a dramatic increase in IL-4 production and Th2 generation. Analysis of RNA and nuclear proteins of CD4(+) T cells 48 It after stimulation revealed that this was due to early IL-4 expression. Interestingly, transient Erk activation resulted in altered AP-1 DNA binding activity and the induction of an AP-1 complex that was devoid of Fos protein and consisted of Jun-Jun dimers. These, data show that in the presence of a strong TCR signal, IL-4 expression can be induced in naive CD4(+) T cells by altering the strength of Erk activation. In addition, these data suggest that TCR-induced Erk activation is involved in the regulation of IL-4 expression by altering the composition of the AP-1 complex and its subsequent DNA binding activity.