我们前期研究证实RANKL过度活化后与破骨细胞表面的RANK结合加速了牙周炎骨吸收的进程。应用RANKL抗体封闭体内RANKL，可明显改善由Th1细胞介导的牙周骨吸收；进一步研究发现Treg细胞活化后牙周组织Th17细胞表达降低，牙周炎症减轻。提示Treg细胞可能通过调节RANK-RANKL信号通路干预Th17细胞或成骨细胞表达RANKL，从而抑制牙周骨吸收。Treg细胞是否通过调控RANKL下游信号通路抑制骨吸收的作用机制迄今未见报道。本项目拟制备P.g诱导的牙周炎动物模型，以牙周炎发展进程中Treg细胞和RANKL的动态变化为切入点，利用Rag2-/-基因缺陷小鼠探讨Foxp3+Helios+Tregs介导RANKL的免疫应答特点，特别是从整体-口腔微环境-细胞层次揭示其发生、发展过程中Foxp3+Treg细胞调控RANKL的具体机制及信号传导途径，渴望为有效防治牙周炎提供确切靶点。

Our previous studies have confirmed that the excessive activation of receptor activator of nuclear factor-kappaB ligand (RANKL) combined with RANK of osteoclasts surface was accelerated periodontal bone resorption process. Application of antibody blocking RANKL in vivo study, it can be significantly improved by Th1 cells mediated periodontal bone resorption; our further study found that the activation of Treg cells decreased the expression of Th17 cells in the periodontal tissues, and periodontal inflammation reduced. Therefore, Treg cells may interfere with Th17 cells or osteoblasts express RANKL by modulating the RANK-RANKL signaling pathway and inhibiting periodontitis. So far have been no reports that the mechanism of whether Treg cells could regulate the downstream signaling pathways of RANKL to inhibit bone resorption. The project intends to make animal models of P.g-induced periodontitis, with the dynamics changes of Tregs and RANKL in development process of periodontitis as a starting point, and then we will take advantage of Rag2-/- mice to discuss that the Foxp3+Helios+Tregs modulate RANKL in characteristic of immune responses. Especially, we will reveal the specific mechanisms and signaling pathways of Foxp3+Treg cell regulation of RANKL from the whole - the oral microenvironment - the cellular level in the development and progression of periodontal disease. Finally, we are eager to provide for the exact targets of the effective prevention and treatment of periodontal disease.