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.