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

Ye Zhang,Ye Zhang,Ye Zhang,Jian-Qi Lian,Gao-Bo Huang,Yi Feng,Yi Feng,Jiali Tan,Jiali Tan,Yajuan Xie,Yajuan Xie,Danfeng Li,Danfeng Li,Xinwei Lyu,Xinwei Lyu,Cheng Hu,Cheng Hu,Wei Kuang,Wei Kuang,Xiao-Fei Yang,Song Xue,Song Xue,Yu Li

doi:10.3389/fimmu.2021.641562

Abstract

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.

Highlights

Periodontitis is an intraoral infection-driven inflammatory disease in periodontal supporting tissues that leads to the pathologic loss of the periodontal ligament and alveolar bone, and even loosening of the teeth [1, 2]
Natural killer-like B (NKB) cells presented the major source of IL-18 in the periodontium of periodontitis patients (Figure 1A)
NKB cells, which could be detected in both peripheral blood and periodontium of humans and mice, were increased in periodontitis patients and P. gingivalis-infected periodontitis murine model

Summary

Introduction

Periodontitis is an intraoral infection-driven inflammatory disease in periodontal supporting tissues that leads to the pathologic loss of the periodontal ligament and alveolar bone, and even loosening of the teeth [1, 2]. Host inflammatory and immune responses to microbial communities alter the subgingival microenvironment, inducing P. gingivalis to be the dominant bacteria in the biofilm. This process breaks the homeostasis between symbiotic microorganisms and the immune system, promotes the development of periodontitis, and triggers systemic diseases [3]. We hypothesized that NKB cells producing IL18 may perform a pivotal role in the immunopathogenesis of periodontitis To test this possibility, we examined NKB cells and secreting cytokines in periodontitis patients, and assessed the ability of IL-18 to evoke periodontal inflammation in P. gingivalis-induced periodontitis mice

Methods

Results

Conclusion