调节性T细胞调控M1/M2型巨噬细胞免疫失衡在牙周炎中的作用研究

Periodontitis is a common disease in oral clinic. Studies have shown that periodontitis is closely associated with immune response, and more and more attentions are payed on the role of regulatory T (Treg) cells and macrophage in periodontitis. Treg cells has been reported to participate in maintainning periodontal tissue homeostasis and repairing tissue injury through IL-10 and TGF-β. Moreover, M1 cell-mediated immune response is enhanced, whereas M2 cell and Treg cell-mediated immune response are weakened in periodontitis. However, the modulation of Treg cells on M1/M2 immune imblance in periodontitis remains unclear. Our previous studies have shown that Treg cells deleption resulted in decreased M2 type cells, increased M1 type cells, and aggravated periodontal bone resorption. We hypothesize that Treg cells could modulate the M1/M2 imblance and play a protective role in periodontitis. Moreover, IL-10 and TGF-β pathways participate in Treg cell modulation. Therefore, this project plans to study the effect of Treg cells on M1 type and M2 type cells in the inflammation and destruction of periodontal tissue, and further explore the effect mechanism in the experimental system which contains P. gingivalis-induced periodontitis mice model, in vivo antibody blocking, and in vitro cell co-culture. The study will provide a new way for the prevention and therapy of periodontitis.

牙周炎是口腔临床的常见病。研究证明牙周炎与免疫应答密切相关，其中调节性T（Treg）细胞和巨噬细胞在牙周炎中的作用备受关注。研究表明Treg细胞可通过IL-10和TGF-β参与维持牙周组织稳态和组织损伤的修复，并且在牙周炎中Treg细胞和M2型巨噬细胞介导的免疫反应减弱，而M1型巨噬细胞介导的免疫反应增强。然而，牙周炎中Treg细胞是否对M1/M2型细胞免疫失衡发挥调节性作用尚无研究报道。课题组前期研究发现；清除Treg细胞后M2型细胞减少，而M1型细胞增加，牙周骨吸收加重。基于此，我们提出假说：Treg细胞可通过IL-10和TGF-β通路调控M1/M2型细胞免疫失衡进而对牙周炎发挥保护作用。我们利用牙龈卟啉单胞菌诱导小鼠牙周炎模型，结合体内抗体阻断、体外细胞共培养等实验系统，研究Treg细胞对M1/M2型巨噬细胞免疫失衡及牙周组织的影响，探讨相关的作用机制，为牙周炎的免疫防治提供新思路。

牙周炎是口腔临床的常见病。研究证明牙周炎与免疫应答密切相关，其中调节性T（Treg）细胞和巨噬细胞在牙周炎中的作用备受关注。有研究表明Treg细胞通过IL-10和TGF-通路上调M2型巨噬细胞的表达，下调M1型巨噬细胞的表达。在牙周炎中存在M1型巨噬细胞介导的免疫反应增强，而M2型巨噬细胞和Treg细胞介导的免疫反应减弱。课题组前期研究发现；清除Treg细胞后M2型细胞减少，而M1型细胞增加，牙周骨吸收加重。基于此，我们提出假说：Treg细胞可调控M1/M2型细胞的免疫失衡进而对牙周炎发挥保护性作用。我们利用牙龈卟啉单胞菌诱导小鼠牙周炎模型，结合体外细胞共培养的实验系统，通过组织病理、实时定量PCR、流式检测等技术研究Treg细胞对M1/M2型细胞免疫失衡及牙周组织损伤的影响。通过研究，我们发现在体内Treg细胞能促进M2型巨噬细胞介导的免疫应答，抑制M1型巨噬细胞介导的免疫应答。然而在体外，诱导分化的Treg细胞却能促进M1型巨噬细胞的分化，抑制M2型巨噬细胞分化。提示在牙周微环境的影响下，Treg细胞作为免疫调节细胞，在牙周炎的发生和发展的不同阶段发挥不同的作用。