Impaired Treg-Mediated Immune Regulation in Peri-Implantitis Lesions and Implant Loss: Insights From Histological and Molecular Analyses

Aim: To evaluate the T regulatory lymphocyte (Treg) profile and its potential contribution to peri-implant tissue destruction during peri-implantitis (PI). Methods: PI granulation tissue and crevicular fluid collected during PI surgical (PI group, n = 23) and explantation (PI-X group, n = 23) therapy, with peri-implant healthy tissue from second-stage surgery (H group, n = 20) as controls, were analysed. The inflammatory infiltrate was characterised by H&E staining. The relative expression of Treg-associated transcription factors and cytokines was assessed by RT-qPCR. Forkhead box P3 (FOXP3) and neuropilin (NPR)-1 were detected by immunohistochemistry, and interleukin (IL)-10, TGF-β1 and IL-35 by ELISA. The clinical parameters, namely probing depth (PD), bleeding on probing (BOP) and vertical defect depth (VDD), were also recorded. Results: PI and PI-X lesions showed up-regulation of FOXP3, HELIOS and IL35B and down-regulation of NRP1 and TGFβ1 mRNA expression, compared to H tissue (p < 0.05). Significantly more FOXP3⁺ cells and significantly less NRP-1⁺ area were detected in PI and PI-X lesions (p < 0.05). IL-35 levels were up-regulated, whereas TGF-β1 levels were down-regulated in PI and PI-X lesions, compared to H samples (p < 0.05). PD and VDD were significantly correlated with the down-regulation of FOXP3 and NRP-1 (p < 0.05). Conclusions: Treg dysfunction and altered cytokine profiles in PI are associated with inflammation and clinical disease severity.