Early growth response transcription factors are required for development of CD4-CD8- thymocytes to the CD4+CD8+ stage
Early growth response transcription factors are required for development of CD4-CD8- thymocytes to the CD4+CD8+ stage
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DOI：
10.4049/jimmunol.168.4.1649
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发表时间：
2002-02-15
影响因子：
4.4
通讯作者：
Wiest, DL
中科院分区：
文献类型：
--
作者：
Carleton, M;Haks, MC;Wiest, DL
未成熟的CD 4（-）CD 8（-）胸腺细胞在β-选择检查点以外进展到CD 4（+）CD 8（+）阶段需要前TCR复合物的活化;然而，很少有DNA结合蛋白作为这些前TCR信号的分子效应物被鉴定。我们在这项研究中证明，早期生长反应（Egr）家族的转录因子的成员是轮胎的信号，促进这种发展的转变的关键效应。具体地，三个Egr家族成员（Egr 1、2和3）的诱导与机智的前TCR活化和CD 4（-）CD 8（-）胸腺细胞的发育相关，超出β-选择检查点。这些Egr因子中的每一种的强制表达能够绕过与有缺陷的前TCR功能相关的胸腺细胞发育中的阻断。然而，Egr fancily成员祈祷在促进胸腺细胞发育方面发挥某种不同的作用，因为通过特定Egr因子的强制表达调节的基因存在差异。最后，使用显性阴性蛋白干扰Egr功能会破坏胸腺细胞从CD 4（-）CD 8（-）到CD 4（+）CD 8（+）阶段的发育。总之，这些数据表明，Egr蛋白在执行由前TCR信号传导启动的分化程序中起重要作用。
Progression of immature CD4(-)CD8(-) thymocytes beyond tire beta-selection checkpoint to the CD4(+)CD8(+) stage requires activation of the pre-TCR complex; however, few of the DNA-binding proteins that serve as molecular effectors of those pre-TCR signals have been identified. We demonstrate in this study that members of the early growth response (Egr) family of transcription factors are critical effectors of tire signals that promote this developmental transition. Specifically, the induction of three Egr family members (Egr1, 2, and 3) correlates witty pre-TCR activation and development of CD4(-)CD8(-) thymocytes beyond the beta-selection checkpoint. Enforced expression of each of these Egr factors is able to bypass the block in thymocyte development associated with defective pre-TCR function. However, Egr fancily members pray play somewhat distinct roles in promoting thymocyte development, because there are differences in the genes modulated by enforced expression of particular Egr factors. Finally, interfering with Egr function using dominant-negative proteins disrupts thymocyte development from the CD4(-)CD8(-) to the CD4(+)CD8(+) stage. Taken together, these data demonstrate that the Egr proteins play an essential role in executing the differentiation program initiated by pre-TCR signaling.