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

Journal of immunology (Baltimore, Md. : 1950) 2020 Apr 15

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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. Copyright © 2020 by The American Association of Immunologists, Inc.

Citation

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. IL-10 Dampens an IL-17-Mediated Periodontitis-Associated Inflammatory Network. Journal of immunology (Baltimore, Md. : 1950). 2020 Apr 15;204(8):2177-2191