γδ T Cells Differentially Regulate Bone Loss in Periodontitis Models

• Published in: Journal of dental research Vol. 101; no. 4; pp. 428 - 436
• Main Authors: Barel, O., Aizenbud, Y., Tabib, Y., Jaber, Y., Leibovich, A., Horev, Y., Zubeidat, K., Saba, Y., Eli-Berchoer, L., Heyman, O., Wilensky, A., Prinz, I., Hovav, A.H.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.04.2022; SAGE PUBLICATIONS, INC
• Subjects: Ablation; Alveolar bone; Alveolar Bone Loss; Animals; Biofilms; Bone Diseases, Metabolic; Bone loss; Cell culture; Disease Models, Animal; Gingiva; Gum disease; Infections; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; Monocytes; Oral infection; Osteoclastogenesis; Osteoclasts; Pathogens; Periodontitis; Periodontitis - pathology; Porphyromonas gingivalis; T-Lymphocytes; Porphyromonas gingivalis; innate immunity; oral mucosa; ligature; osteoclasts; periodontitis
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/00220345211042830

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.