Gundappa Saha
| Gundappa Saha |
Gundappa Saha1, Xiaofei Li1, Melanie Genoula1, Lu Li2, Patricia I Diaz2, George Hajishengallis1
1Department of Basic and Translational Sciences, University of Pennsylvania, School of Dental Medicine; 2Department of Oral Biology, University of Buffalo
Introduction
Periodontal Disease (PD) is an inflammatory condition which primarily affects the periodontium (tooth-supporting tissues), and this study mainly focusses on the role of IL-22 in mediating periodontal tissue homeostasis at steady state which has not been investigated yet. The context-dependent role of IL-22 in diseases lead us to investigate the behavior in health as well. Owing to the involvement of both mucosal and bone tissue in periodontium, PD is a unique model to study the role of IL-22 in both health and disease. Our primary hypothesis in this study is that IL-22 is required in periodontal health for maintaining steady-state homeostasis.
Methods
To address our hypothesis, we have planned to analyze the distance from the cement-enamel junction (CEJ) to alveolar bone crest (ABC) as a measure of bone height in 10-weeks-old IL-22–/– mice vs IL-22+/+ littermate controls under steady state to assess natural periodontitis. We have investigated bacterial loads and characterize the microbiota composition using 16S rRNA sequencing to assess the effect of IL-22 deficiency. In addition, we did bulk RNA sequencing analyses of IL-22-deficient gingival tissue cells to further obtain transcriptomic insights in relation to IL-22 as a homeostatic molecule in health. For establishment of natural periodontitis, we are performing similar studies in longitudinal mode (e.g., including 18-week-old mice).
Results
10-week-old IL-22–/– mice had increased CEJ-ABC distance vs age-matched IL-22+/+ littermate controls, thus indicating increased bone loss which further increased in 18-week-old mice. We observed significant changes in the microbiota composition in IL-22–/– mice vs IL-22+/+ controls and increased bacterial load in the former group, indicating dysbiotic alterations. In addition, we found increase in IL-17 expression and antimicrobial proteins in IL-22–/– mice vs IL-22+/+ littermate controls.
Conclusion
IL-22 deficiency results in increased IL-17 expression and bone loss that is associated with dysbiosis of the periodontal microbiota. The increased expression of antimicrobial proteins in the IL-22-deficient periodontium might represent a compensatory mechanism to mitigate the increased microbial growth and dysbiosis.