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中科院在调节性T细胞领域取得重要突破摘要 : 中国科学院微生物研究所张福萍课题组最近在免疫学和实验医学杂志Journal of Experimental Medicine发表的文章发现，胸腺中E-蛋白的动态变化对调控Treg细胞的发育起了决定性的作用。
Treg细胞表面标志 Treg细胞是维持机体免疫稳态中至关重要的一类细胞，Treg细胞的缺失会导致人类严重的致死性自身免疫病。Treg功能过强又会导致肿瘤和慢性感染性疾病的发生。长期以来Treg细胞的发育机制仍不清楚，使临床对Treg细胞的应用受到了很大的限制。 中国科学院微生物研究所张福萍课题组最近在免疫学和实验医学杂志Journal of Experimental Medicine发表的文章发现，胸腺中E-蛋白的动态变化对调控Treg细胞的发育起了决定性的作用。在这个过程中，TCR(T cell receptor,T细胞受体)信号的强弱决定了E-蛋白的水平,而E-蛋白的水平是决定胸腺中双阳性细胞是发育成常规CD4阳性T淋巴细胞还是Treg细胞的重要因素。E-蛋白的水平高低是决定对Treg细胞发育至关重要的两个转录因子c-Rel 和STAT5是否被激活的关键。因此可以通过调节E-蛋白的表达水平来调节c-Rel或STAT5 的激活，从而达到调节Treg细胞产生的目的。 这一发现使人们从根本上认识Treg细胞在胸腺中发育的机制，为调控机体的免疫反应提供了重要的理论基础和手段。对自身免疫病的治疗和传染病的防控具有重要的指导意义。此外，由于Treg细胞和Th17细胞(辅助t细胞17)有互相调控的关系，此发现也将为研究Treg细胞和Th17细胞的互相转化提供基础。张福萍课题组的高平助理研究员为文章的第一作者，张福萍为文章的通讯作者。 原文标题：Dynamic changes in E-protein activity regulate T reg cell development 原文摘要：E-proteins are TCR-sensitive transcription factors essential for intrathymic T cell transitions. Here, we show that deletion of E-proteins leads to both enhanced peripheral TGF-β–induced regulatory T (iT reg) cell and thymic naturally arising T reg cell (nT reg cell) differentiation. In contrast, deletion of Id proteins results in reduced nT reg cell differentiation. Mechanistic analysis indicated that decreased E-protein activity leads to de-repression of signaling pathways that are essential to Foxp3 expression. Decreased E-protein binding to an IL-2Rα enhancer locus facilitated TCR-induced IL-2Rα expression. Similarly, decreased E-protein activity facilitated TCR-induced NF-κB activation and generation of c-Rel. Consistent with this, microarray analysis indicated that cells with E-protein depletion that are not yet expressing Foxp3 exhibit activation of the IL-2 and NF-κB signaling pathways as well as enhanced expression of many of the genes associated with Foxp3 induction. Finally, studies using Nur77-GFP mice to monitor TCR signaling showed that TCR signaling strength sufficient to induce Foxp3 differentiation is accompanied by down-regulation of E-protein levels. Collectively, these data suggest that TCR stimulation acts in part through down-regulation of E-protein activity to induce T reg cell lineage development.