内源性RelB对Treg分化和自稳平衡的负向调控分子机制研究

Regulatory T cells (Treg) play critical roles in autoimmune tolerance. The molecular mechanisms of Treg differentiation and homeostasis is one of the important questions in this field. Although several factors have been revealed to positively control Treg differentiation and homeostasis, it has been largely unknown about its negative regulation. We find the T cell intrinsic RelB plays an important negative regulation for Treg differentiation and homeostasis. Based on this, we will further explore the mechanism of RelB regulating the Treg differentiation and homeostasis from two aspects. First, to study if the RelB regulates the differentiation of Treg through inhibiting the c-Rel or other transcription factors of Foxp3. Second, to study if the RelB regulates the homeostasis of Treg through STAT5 and / or Bim. At the same time, we'll study the influence of RelB on the Treg suppressive function in vitro and in vivo. This study will reveal an novel role of RelB in Treg differentiation and homeostasis and also provide us new molecular targets for diagnosis and therapy of autoimmune diseases.

调节性T细胞（Treg）在自身免疫耐受中发挥着重要的作用。Treg的分化和自稳平衡的分子机制是本领域重要的科学问题之一。近年来的研究揭示了许多调控Treg分化和自稳平衡的正调控因子，但是对于Treg的负向调控则知之甚少。我们的前期研究结果表明，T细胞内源性的RelB对于Treg的胸腺分化和外周自稳平衡起到了重要的负向调控作用。在本项目中我们主要以此为基础，从两个方面对RelB的调控机制进行深入研究：（1）RelB是否通过抑制c-Rel或其他Foxp3转录因子的活性负向调控Treg的分化；（2）RelB是否通过STAT5通路和/或Bim通路负向调控Treg的自稳平衡。同时，我们还将利用体外和体内Treg抑制实验，探索RelB对Treg功能的影响。该研究将从一个新的角度，增加对Treg分化和自稳平衡分子调控机制的理解，为自身免疫病的诊断和治疗提供新的分子靶点和科学依据。

调节性T细胞（Treg）在自身免疫耐受中发挥着重要的作用。Treg的分化和自稳平衡的分子机制是本领域重要的科学问题之一。近年来的研究揭示了许多调控Treg分化和自稳平衡的正调控因子，但是对于Treg的负向调控则知之甚少。我们的前期研究结果表明，RelB缺失后外周的Treg比例显著升高，提示RelB可能是Treg分化和自稳平衡的负调控因子。研究表明，外源性RelB对Treg自稳平衡具有负向调控作用，外源性RelB缺失能够通过抑制p27kip1和LeptinR的表达水平促进Treg细胞在外周的增殖。同时研究结果发现，RelB缺失后对Treg的分化以及抑制功能没有影响。