Natural killer-like B (NKB) cells, which are newly identified immune subsets, reveal a critical immunoregulatory property in the eradication of microbial
infection via 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 Porphyromonas gingivalis (P. gingivalis)-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. In vitro
IL-18 stimulation promoted proinflammatory
cytokine production in periodontal ligament cells. P. gingivalis
infection induced elevation of
IL-18 receptor in periodontium in a
periodontitis murine model.
IL-18 neutralization not only suppressed P. gingivalis-induced alveolar
bone resorption, but also inhibited recruitment of
antigen-non-specific inflammatory cells into the periodontium, probably via 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 P. gingivalis
infection. These findings might be relevant to the development of
immunotherapies for
periodontitis.