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An alternative NFAT-activation pathway mediated by IL-7 is critical for early thymocyte development

机译:IL-7介导的另一种NFAT激活途径对于早期胸腺细胞发育至关重要

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摘要

Interleukin 7 (IL-7) has a critical role in the development of early CD4-CD8-double-negative (DN) thymocytes. Although the transcription factor STAT5 is an important component of IL-7 signaling, differences in the phenotypes of mice deficient in STAT5, IL-7, IL-7 receptor alpha (IL-7rα) or the kinase Jak3 suggest the existence of STAT5-independent IL-7 signaling. Here we found that IL-7-Jak3 signals activated the transcription factor NFATc1 in DN thymocytes by phosphorylating Tyr371 in the regulatory region of NFATc1. This NFAT-activation pathway was critical for the survival and development of DN thymocytes, as deficiency in NFATc1 blocked thymocyte development at the DN1 stage, leading to T cell lymphopenia. In addition, our results demonstrated a cooperative function for NFATc1 and STAT5 in guiding thymocyte development in response to IL-7 signals.
机译:白细胞介素7(IL-7)在早期CD4-CD8-双阴性(DN)胸腺细胞的发育中起关键作用。尽管转录因子STAT5是IL-7信号转导的重要组成部分,但缺乏STAT5,IL-7,IL-7受体α(IL-7rα)或激酶Jak3的小鼠的表型差异表明存在STAT5依赖性IL-7信号传导。在这里,我们发现IL-7-Jak3信号通过使NFATc1调控区域中的Tyr371磷酸化而激活了DN胸腺细胞中的转录因子NFATc1。该NFAT激活途径对于DN胸腺细胞的生存和发育至关重要,因为NFATc1的缺乏会阻止DN1阶段胸腺细胞的发育,从而导致T细胞淋巴细胞减少。此外,我们的结果证明NFATc1和STAT5在引导胸腺细胞响应IL-7信号方面具有协同作用。

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