转录因子E蛋白（E2A/HEB）在调节胸腺中T细胞的发育中起着关键性的作用。我们的前期工作表明E蛋白既调控Th17细胞的分化，也参与调节nTreg细胞的发育。但E蛋白对维持Treg细胞的功能和稳定性是否重要以及E蛋白在以上过程中的机制是什么，仍不清楚。本项目通过在Foxp3表达后中敲除E蛋白，首先研究在Treg细胞中敲除E蛋白后是否仍然会影响Treg细胞的分化；利用不同的炎症疾病模型如Transfer colitis, EAE, DSS肠炎等，研究在Treg细胞中敲除E蛋白后对Treg功能及稳定性的影响； 为阐明E蛋白调节Treg细胞功能和稳定性的机制，将利用RNA-seq和染色质免疫沉淀等方法，发现E蛋白调控Treg细胞功能和稳定性的靶点，并对其靶点进行验证。 项目的研究将更深入阐明在炎症环境中Treg细胞发挥功能的机制，对通过操纵Treg细胞的免疫治疗有重要意义。

E proteins (E2A/HEB) are transcription factors that are essential for T cell development in thymus, our previous finding showed that E proteins regulate Treg cell development. However, whether E protein plays a role in maintaining Treg cell function and stability is still unclear. By crossing the E2Af/fHEBf/f mice with Fopx3-GFP-Cre-Rosa26-Stop-YFP mice, we propose to address the effect of E protein on Treg cells in a comprehensive fashion. First, by knocking out E protein specifically in Treg cells after Foxp3 expression, we will investigate if E protein is still has an effect on Treg cell development, then, the role of E protein in the maintaining Treg cell function and stability will be addressed by using different disease model such as EAE, transfer colitis and DSS colitis ect. Finally, the relevance mechanism of E protein that modulate Treg cell function and stability will determined by RNA-Seq and ChIP study. New target of E protein will screened from the RNA-Seq data and will be verified. We believe this project will provide novel insights into an unexplored area of E protein biology that will not only fuel a better understanding of Treg cell development, but will also facilitate the development of novel approaches to therapeutic manipulate Treg cells.