Department of Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Center for Oral and Systemic Diseases, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
J Immunol. 2020 Apr 15;204(8):2177-2191. doi: 10.4049/jimmunol.1900532. Epub 2020 Mar 13.
Emerging evidence suggests comprehensive immune profiling represents a highly promising, yet insufficiently tapped approach to identify potentially prognostic signatures for periodontitis. In this report, we agnostically identified a periodontitis-associated inflammatory expression network with multiple biomarkers identified within gingival crevicular fluid samples from study participants by applying principal component analysis. We identified an IL-17-dominated trait that is associated with periodontal disease and is inversely modified by the level of IL-10. IL-10 mitigated chemokine CXCL5 and CXCL1 expressions in IL-17-stimulated peripheral blood monocytic cells and peripheral blood monocytic cell-derived macrophages. -deficient mice presented more bone loss, which was associated with more and IL-17-mediated chemokine and cytokine expression at the transcriptional levels in comparison with control wild-type mice in both the -induced experimental murine periodontitis and ligature-induced alveolar bone-loss models. The dampening effect of IL-10 on the excessive signaling of IL-17 appeared to be mediated by innate immune cells populations rather than by gingival epithelial cells, which are the major cell target for IL-17 signaling. Additionally, elevated IL-17 response in -deficient mice specifically elicited an M1-skewing macrophage phenotype in the gingiva that was associated with the advanced bone loss in the ligature model. In summary, IL-17 dominated an inflammatory network characteristic of periodontitis, and IL-10 dampens this excessive IL-17-mediated periodontitis trait.
新出现的证据表明，全面的免疫分析代表了一种极具前景但尚未充分利用的方法，可以确定牙周炎的潜在预后特征。在本报告中，我们通过应用主成分分析，从研究参与者的牙龈沟液样本中，发现了一个与牙周炎相关的炎症表达网络，其中包含多个生物标志物。我们发现了一种由 IL-17 主导的特征，它与牙周病有关，并且受到 IL-10 水平的反向调节。IL-10 减轻了 IL-17 刺激的外周血单核细胞和外周血单核细胞衍生的巨噬细胞中趋化因子 CXCL5 和 CXCL1 的表达。IL-10 缺陷型小鼠表现出更多的骨丢失，与对照野生型小鼠相比，在 - 诱导的实验性小鼠牙周炎和结扎诱导的牙槽骨丢失模型中，其转录水平的 和 IL-17 介导的趋化因子和细胞因子表达更多。与牙龈上皮细胞相比，IL-10 对 IL-17 过度信号的抑制作用似乎是由先天免疫细胞群介导的，而不是由其介导的，后者是 IL-17 信号的主要细胞靶标。此外，- 缺陷型小鼠中升高的 IL-17 反应特异性地在牙龈中引发了一种 M1 偏向的巨噬细胞表型，这与结扎模型中的晚期骨丢失有关。总之，IL-17 主导了牙周炎的炎症网络特征，而 IL-10 抑制了这种过度的 IL-17 介导的牙周炎特征。
