调节性T细胞（Treg）对维持自身免疫稳定至关重要，转录因子Foxp3不仅是调节性T细胞的特异性标志基因，也对Treg细胞的发育和功能都起着极为关键的作用。与小鼠不同，人Treg细胞中存在两种表达量接近的Foxp3亚型，即Foxp3a和Foxp3b剪切体，两种亚型的区别在于Foxp3b剪切体不含2号外显子。目前，Foxp3b剪切体在调节性T细胞中的功能还不清楚，我们的前期结果显示Foxp3a和Foxp3b剪切体有不同的DNA结合特性。本项目拟通过构建Foxp3的2号外显子敲除小鼠，从分子、细胞及动物多个水平，探索Foxp3b剪切体的生物学功能。该研究将深化我们对人调节性T细胞了解，研究结果可能为多种自身免疫疾病、感染性疾病及癌症等提供新的治疗策略。

Regulatory T cells (Tregs) are a specialized subpopulation of CD4+ T cells that play a pivotal role in the maintenance of immune homeostasis. The transcription factor Foxp3 is not only a specific marker of regulatory T cells but also indispensable for their differentiation and suppressive function. Unlike the mouse Foxp3, that only expresses a single mRNA in Tregs, two Foxp3 splicing forms, Foxp3a and Foxp3b are present in the human Tregs. The difference between the two subtypes is that Foxp3b does not contain exon 2. It is not yet clear whether Foxp3b process any function in regulatory T cells. Our preliminary results have shown that Foxp3a and Foxp3b have different DNA-binding properties. This project aims to explore the biological functions of the Foxp3b by generating Foxp3 exon 2 knockout mice. This study will provide the new insight of understanding of human regulatory T cells, which might have important implications in both autoimmune pathogenesis and the tumor therapy.