IL-10 Dampens an IL-17–Mediated Periodontitis-Associated Inflammatory Network
Lu Sun, Mustafa Girnary, Lufei Wang, Yizu Jiao, Erliang Zeng, Kyle Mercer, Jinmei Zhang, Julie T. Marchesan, Ning Yu, Kevin Moss, Yu L. Lei, Steven Offenbacher, Shaoping Zhang
Abstract
Abstract 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. Il10-deficient mice presented more bone loss, which was associated with more Il17 and IL-17–mediated chemokine and cytokine expression at the transcriptional levels in comparison with control wild-type mice in both the Porphyromonas gingivalis–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 Il10-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.