Natural Killer-Like B Cells Secreting Interleukin-18 Induces a Proinflammatory Response in Periodontitis

Abstract

Natural killer-like B (NKB) cells, which are newly identified immune subsets, reveal a critical immunoregulatory property in the eradication of microbial infection <i>via</i> the secretion of interleukin (IL)-18. For the first time, this study investigated the role of NKB cells in secreting IL-18 in the pathogenesis of periodontitis. In this study, NKB cells' percentage and IL-18 concentration in peripheral blood and periodontium in periodontitis patients was measured using flow cytometry and ELISA. The role of IL-18 in regulating periodontal inflammation was examined in a <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>)-induced periodontitis murine model. Peripheral and periodontal-infiltrating CD3^-CD19⁺NKp46⁺ NKB cells, which were the main source of IL-18, were elevated and correlated with attachment loss in periodontitis patients. <i>In vitro</i> IL-18 stimulation promoted proinflammatory cytokine production in periodontal ligament cells. <i>P. gingivalis</i> infection induced elevation of IL-18 receptor in periodontium in a periodontitis murine model. IL-18 neutralization not only suppressed <i>P. gingivalis</i>-induced alveolar bone resorption, but also inhibited recruitment of antigen-non-specific inflammatory cells into the periodontium, probably <i>via</i> dampening expressions of cytokines, chemokines, and matrix metalloproteinases. NKB cells secreting IL-18 appeared to be an important mediator in the inflammatory response following intraoral <i>P. gingivalis</i> infection. These findings might be relevant to the development of immunotherapies for periodontitis.