B10细胞在改善牙周炎症中牙槽骨破坏的作用和相关机制研究

Unbanlanced immune response in periodontal lesion is the important pathogenesis of alveolar bone resorption. How to prevent the aggressive immune response is the main problem unsolved in periodontal treatment. Many studies demonstrated that B10 cells with a regulatory function play a key role in immune system balance, restraining the excessive inflammatory responses. Pivotal to B10 function is interleukin-10 (IL-10). Our prior study showed there was significant different expression of B10 in the periodontal tissue between periodontitis group and healthy control, which suggests the important role of B10 in the periodontitis. In this study, the luciferase-labeled B10 cells will be activated and expanded, then transfer to the periodontal lesion of B deficient or IL-10 knockout mice. The dynamic function of B10 cells will be observed by IVIS imaging technique. This study is to explore the role and mechanism of B10 cells in the amelioration of periodontal bone resorption and inflammation, and also identify factors that control local B10 expansion and aptosis by TLR signal pathway and co-stimulatory agent injection. As we know, it is the first time to propose a new concept “ B10 cells with immune downregulation in the amelioration of alvelor bone resorption” It is expected to provide the theoretical base of a novel treatment option to dampen the exaggerated immune-mediated bone resorption in periodontitis.

牙周病损部位过度的免疫反应是牙槽骨发生病理性破坏的重要因素，如何限制宿主的过度免疫反应是目前牙周炎治疗研究的难点。以IL-10为功能核心的调节性B细胞（B10）在维持免疫平衡中起重要作用，主要通过释放IL-10负向调节免疫反应，从而抑制炎症、减少组织破坏。课题组发现牙周病损部位B10细胞的表达与健康组织存在显著差异，推测B10细胞在牙周炎中可能起重要作用。本项目拟活化、扩增荧光素酶标记的抗原特异性B10细胞，建立B细胞缺陷和IL-10敲除小鼠牙周炎模型，通过移植B10细胞，利用活体成像技术，研究B10细胞在牙周炎症中负向调节免疫反应的作用和机制，并通过Toll样信号和协同刺激剂来研究牙周病损部位B10细胞的增殖和凋亡的调控因素，探索解决由于过度免疫反应导致的牙槽骨破坏的科学难题。本项目首次提出以B10细胞为基础的负向免疫调节抑制牙槽骨破坏的新概念，为临床牙周炎的免疫治疗新方法奠定理论基础。

以IL-10为核心的调节性B细胞（B10）在维持免疫平衡中起重要作用。IL-10的释放可以负向调节免疫反应，从而抑制炎症，减少组织破坏。本研究证实在牙周组织中，炎症和B10的形成密切相关, 说明B10可能在牙周炎的进展中起重要作用。B10细胞是牙周炎症组织中分泌IL-10的主要免疫细胞。已证实局部移植高表达IL-10的淋巴细胞群能抑制小鼠实验性牙周炎的牙槽骨吸收、CD4+T细胞的表达、RANKL及IL-1β表达，能够抑制中性粒细胞的浸润和减少表达RANKL的中性粒细胞数量，以及B10细胞主要通过IL-10对Tregs细胞产生诱导作用，但是细胞间接触也起到协同效应。同时B10细胞和成骨的相关因子也有密切关系。这些结果说明了B10细胞在抑制炎症、减少牙槽骨破坏起重要作用，其和各免疫细胞的交互作用标志着B10细胞在保持牙周稳态中的重要作用，为临床治疗牙周炎提供新的方向。