γδ T Cells Differentially Regulate Bone Loss in Periodontitis Models

Abstract

γδ T cells are nonclassical T lymphocytes representing the major T-cell population at epithelial barriers. In the gingiva, γδ T cells are enriched in epithelial regions adjacent to the biofilm and are considered to regulate local immunity to maintain host-biofilm homeostatic interactions. This delicate balance is often disrupted resulting in the development of periodontitis. Previous studies in mice lacking γδ T cells from birth ( Tcrd-/- mice) examined the impact of these cells on ligature-induced periodontitis. Data obtained from those studies proposed either a protective effect or no impact to γδ T cells in this setting. Here, we addressed the role of γδ T cells in periodontitis using the recently developed Tcrd-GDL mice, enabling temporal ablation of γδ T cells. Specifically, the impact of γδ T cells during periodontitis was examined in 2 modalities: the ligature model and the oral infection model in which the pathogen Porphyromonas gingivalis was administrated via successive oral gavages. Ablation of γδ T cells during ligature-induced periodontitis had no impact on innate immune cell recruitment to the ligated gingiva. In addition, the number of osteoclasts and subsequent alveolar bone loss were unaffected. However, γδ T cells play a pathologic role during P. gingivalis infection, and their absence prevented alveolar bone loss. Further analysis revealed that γδ T cells were responsible for the recruitment of neutrophils and monocytes to the gingiva following the exposure to P. gingivalis. γδ T-cell ablation also downregulated osteoclastogenesis and dysregulated long-term immune responses in the gingiva. Collectively, this study demonstrates that whereas γδ T cells are dispensable to periodontitis induced by the ligature model, they play a deleterious role in the oral infection model by facilitating pathogen-induced bone-destructive immune responses. On a broader aspect, this study highlights the complex immunopathologic mechanisms involved in periodontal bone loss.

Role of Interleukin-17A in the Pathomechanisms of Periodontitis and Related Systemic Chronic Inflammatory Diseases

“…This lone-term chronic inflammatory response results in the absorption of alveolar bone by osteoclasts and the degradation of periodontal membrane fibers by MMPs. The ratio of Th17/Treg cells in gingival tissue and peripheral blood of patients with chronic periodontitis was significantly higher than that of healthy people ( 70 ), and the number of γδT cells in gingival tissue was also higher than that of healthy people ( 71 ). As what mentioned before, both Th17 cells and γδ T cells are the cell sources of IL-17A, suggesting that the expression level of IL-17A in periodontal region of patients with chronic periodontitis is significantly higher than that of healthy people, which has been confirmed by many studies in recent years ( 72 – 74 ).…”

C‐reactive protein perturbs alveolar bone homeostasis: An experimental study of periodontitis and diabetes in the rat

“…However, a recent study reported that the kinetics of bone loss induced by ligature and oral gavage differed considerably. In contrast to oral infection, the effects of ligation on the host may be less systemic (Barel et al, 2021). In addition, although our modelling process was standardized, ligature inevitably causes a small amount of mechanical damage, which is a limitation of our model.…”

γδT cells in oral tissue immune surveillance and pathology

“…Of late, a study by Bare et al. may give us some novel insights into the unique role of γδ17T cells in periodontitis ( 86 ). Although their findings identified again that γδ17T cells are not necessary for bone loss brought on by the ligature-induced periodontitis, they surprisingly found that γδ17T cells promote periodontal damage driven on by oral infection with Porphyromonas gingivalis .…”