Riera-Sans Lluís, Behrens Axel
London Research Institute, Cancer Research, Mammalian Genetics Laboratory, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London, UK.
J Immunol. 2007 May 1;178(9):5690-700. doi: 10.4049/jimmunol.178.9.5690.
c-Jun is a member of the AP-1 family of transcription factors, the activity of which is strongly augmented by TCR signaling. To elucidate the functions of c-Jun in mouse thymic lymphopoiesis, we conditionally inactivated c-Jun specifically during early T cell development. The loss of c-Jun resulted in enhanced generation of gammadelta T cells, whereas alphabeta T cell development was partially arrested at the double-negative 3 stage. The increased generation of gammadelta T cells by loss of c-Jun was cell autonomous, because in a competitive reconstitution experiment the knockout-derived cells produced more gammadelta T cells than did the control cells. C-jun-deficient immature T cells failed to efficiently repress transcription of IL-7Ralpha, resulting in augmented IL-7Ralpha mRNA and surface levels. Chromatin immunoprecipitation assays revealed binding of c-Jun to AP-1 binding sites present in the IL-7Ralpha promoter, indicating direct transcriptional regulation. Thus, c-Jun controls the transcription of IL-7Ralpha and is a novel regulator of the alphabeta/gammadelta T cell development.
c-Jun是转录因子AP-1家族的成员，其活性会被TCR信号强烈增强。为了阐明c-Jun在小鼠胸腺淋巴细胞生成中的功能，我们在早期T细胞发育过程中特异性地条件性失活了c-Jun。c-Jun的缺失导致γδ T细胞生成增加，而αβ T细胞发育在双阴性3阶段部分停滞。c-Jun缺失导致γδ T细胞生成增加是细胞自主性的，因为在竞争性重建实验中，敲除来源的细胞比对照细胞产生更多的γδ T细胞。c-Jun缺陷的未成熟T细胞未能有效抑制IL-7Rα的转录，导致IL-7Rα mRNA和表面水平增加。染色质免疫沉淀分析显示c-Jun与IL-7Rα启动子中存在的AP-1结合位点结合，表明存在直接转录调控。因此，c-Jun控制IL-7Rα的转录，是αβ/γδ T细胞发育的新型调节因子。
