β-防御素2在IL-1β介导的活动性牙周炎中的免疫调控功能及其分子机制

免疫炎症调控失衡是活动性牙周炎发生与发展的重要原因。课题组及同行前期证实IL1β是牙周炎进展的关键调节因子，但IL1β在牙周炎进展中的表达调控机制仍不清楚。课题组进一步发现防御素（hBD2）与调控Th17/Treg平衡的关键因子TGFβ呈显著负相关。另外，文献报道hBD2能够参与Th17/Treg平衡及IL1β表达的调控并且Th17可通过IL17/IL21等激活IL1β的表达，但是hBD2在其中具体、准确的免疫学功能与调节机制仍不清楚。因此，我们提出“hBD2可通过TGFβ调节Th17/Treg平衡，进而双重调控IL1β表达，最终实现对牙周炎进展有效调节”的科学假说。为验证该假说，我们将构建牙周炎进展体外、体内研究模型，深入研究分析hBD2如何分化调控Th17/Treg平衡进而调节IL1β表达并最终影响牙周炎进展。研究结果将为牙周炎进展发病机理提供新的科学依据，并为牙周炎防治提供新思路。

The imbalance of host inflammatory/immune response is the main cause of periodontal tissue destruction in the“active period” of periodontitis. The findings from our preliminary work and various researches revealed that IL-1β is the key factor in regulating the inflammatory/immune process of periodontitis, however, the underlying mechanisms were not well understood. Another projects of our group showed a negative correlation between hBD2 and TGF-β, a key regulator of the Th17/Treg balance, moreover, latest research findings also demonstrated that defensins are capable to regulate both the balance of Th17/Treg and IL-1β expression, while IL-17 and IL-22 produced by Th17 cells could enhance inflammation by stimulating the secretion of IL-1β. However, the exact work mechanism of hBD2 in periodontitis progression remains to be elucidated and the links between these factors also needed to be explored. Thus, we hypothesized that “hBD2-TGF-β-Th17/Treg-IL-1β signaling axis would play a dual and important role in the process of periodontitis progression”. In order to verify the hypothesis and explore the mechanism, in vitro and in vivo experimental models of periodontitis progression will be established to investigate how hBD2 regulateTh17/Treg and adjust the expression and function of IL-1β in the “active period” of periodontitis. This comprehensive study will not only provide new insights into mechanisms of periodontitis progression, but also create a new paradigm for the development of new therapeutic approaches in prevention and treatment of periodontitis progression.