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 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.

Inflammasomes and the IL-1 Family in Bone Homeostasis and Disease

“…Additionally, wild-type mice challenged with P . gingivalis had elevated expression of Il1b and Il18 mRNA in the periodontium [ 92 ], which was also noted by others [ 136 ]. Bruton’s tyrosine kinase (BTK) is already known to regulate osteoclast maturation and fusion [ 137 , 138 ], and was shown to also modulate the NLRP3 inflammasome, through interaction with ASC and NLRP3 [ 139 ].…”

Spectrum effect correlation of yangyin tongnao granules on cerebral ischemia-reperfusion injury rats

“…IL-18 is an important inflammatory factor in the IL-1 family, which is predominantly secreted by epithelial cells, dendritic cells, and macrophages ( Dinarello, 2002 ). IL-18 is the main cytokine downstream of NLRP3 inflammasome that can be released by inflammasome at the time of inflammation ( Zhang et al, 2021 ). As the downstream indicators of the JAK2/STAT3 signaling pathway ( Raible et al, 2014 ; Qin et al, 2019 ; Sun et al, 2020 ), IL-18 and TNF-α are the key factors in the inflammatory response ( Zhou et al, 2016 ; Li et al, 2018 ).…”

Classifying Integrated Signature Molecules in Macrophages of Rheumatoid Arthritis, Osteoarthritis, and Periodontal Disease: An Omics-Based Study

“…Therefore dysregulation of the IL-18 signaling pathway plays a major role in RA [ 69 ] and OA [ 70 ]. The IL-18 signaling pathway also plays an important role in pro-inflammatory cytokine production in PD, which is the main cause of alveolar bone loss in the presence of PG [ 71 ]. Therefore, even though IER3 and RGS16 are non-hub genes, it is crucial to understand their role in three macrophage conditions.…”