Mucosal Immunol. 2025 Jun 27:S1933-0219(25)00068-6. doi: 10.1016/j.mucimm.2025.06.008. Online ahead of print.
ABSTRACT
Poorly controlled diabetes significantly transforms periodontal disease from manageable to advanced, affecting millions worldwide, yet the mechanisms driving this destructive synergy remain unclear. To investigate these pathological interactions, we generated single-cell RNA sequencing profiles of diabetic periodontal tissue, revealing γδ T-cells as previously unrecognized central mediators of diabetes-enhanced periodontal destruction. Flow cytometry validation confirmed significant expansion of IL-17A-producing γδ T-cells in diabetic versus normoglycemic mice, with parallel findings of elevated IL-17A + cells in human diabetic periodontal specimens. Selective γδ T-cell inhibition substantially reversed diabetes-enhanced periodontal destruction while minimally affecting normoglycemic controls and returned neutrophil infiltration to normoglycemic levels. scRNAseq identified other factors, including greater neutrophil polarization toward a pro-inflammatory phenotype and loss of Tregs. These findings point to unique aspects of diabetes-induced dysregulation and implicate γδ T-cells as a driving factor in this process. The results also point γδ to T-cells as a therapeutic target in periodontitis and other diabetic complications.
PMID:40582570 | DOI:10.1016/j.mucimm.2025.06.008