Immunological link between periodontitis and type 2 diabetes deciphered by single‐cell RNA analysis

Abstract Background Type 2 diabetes mellitus (DM) is a complex metabolic disorder that causes various complications, including periodontitis (PD). Although a bidirectional relationship has been reported between DM and PD, their immunological relationship remains poorly understood. Therefore, this study aimed to compare the immune response in patients with PD alone and in those with both PD and DM (PDDM) to expand our knowledge of the complicated connection between PD and DM. Methods Peripheral blood mononuclear cells were collected from 11 healthy controls, 10 patients with PD without DM, and six patients with PDDM, followed by analysis using single‐cell RNA sequencing. The differences among groups were then compared based on intracellular and intercellular perspectives. Results Compared to the healthy state, classical monocytes exhibited the highest degree of transcriptional change, with elevated levels of pro‐inflammatory cytokines in both PD and PDDM. DM diminished the effector function of CD8+ T and natural killer (NK) cells as well as completely modified the differentiation direction of these cells. Interestingly, a prominent pathway, RESISTIN, which is known to increase insulin resistance and susceptibility to diabetes, was found to be activated under both PD and PDDM conditions. In particular, CAP1 + classical monocytes from patients with PD and PDDM showed elevated nuclear factor kappa B‐inducing kinase activity. Conclusions Overall, this study elucidates how the presence of DM contributes to the deterioration of T/NK cell immunity and the immunological basis connecting PD to DM.