树突状细胞（DC）异常迁移会导致炎症反应和自身免疫疾病。β-arrestins是机体分布广泛的多功能接头蛋白，在多种免疫细胞和自身免疫疾病中发挥调节作用，而β-arrestins对DC功能的调节未见报道。我们最新发现随着DC迁移能力增强，β-arrestin 2表达下调；敲除该基因的DC迁移能力显著增强；并且在全身或者DC条件敲除鼠的脾脏和淋巴结中迁移型DC细胞显著增多，这一现象与DC特异性转录因子Zbtb46基因敲除鼠脾脏和淋巴结中现象一致。基于此，我们提出β-arrestin 2通过与Zbtb46相互作用，负调节DC细胞的迁移，并最终导致自身免疫疾病发生的工作假说，拟基于蛋白-蛋白相互作用、元代DC细胞迁移、以及整体动物疾病模型、临床样品分析四个层面开展研究，揭示β-arrestins在调控DC迁移及自身免疫疾病中的功能及机制，为自身免疫疾病的发病机制和治疗提供新的线索。

Previous studies have demonstrated that abnormally altered migration ability of dendritic cells (DC) leads to the development of inflammatory and autoimmune diseases. β-arrestin 2, a multi-functional adaptor protein, ubiquitously expressed in all tissues, have been reported to involve in modulating functions of many kinds of immunocytes and autoimmune diseases. However, it is still largely unknown about the role of β-arrestins in DCs’ function. Recently, we found that in the matured DCs with increased migration, the expression of β-arrestin 2 was upregulated significantly. And at the same time, deficiency of β-arrestin 2 leads to significantly increased migration of DCs. What’s more, the number of the migratory DCs in spleen and lymph nodes is much higher in β-arrestin 2 knockout mice than that in WT mice. A similar phenomenon has been reported in Zbtb46 knockout mice. Taken together, we assume that β-arrestin 2 interacts with Zbtb46 and negatively regulate the migration of DCs, finally modulation the pathogenesis of autoimmune diseases. We will use protein-protein interaction assay, primary DC migration assay, conditional knockout mice, and clinical samples analysis to confirm our hypothesis. For the purpose of providing new insights into the mechanisms underlying the development of autoimmunity and suggesting possible drug targets for disease therapy.