Epithelial Cell Control of Adaptive Immune Plasticity in Periodontal Disease

Abstract

Abstract In periodontal disease (PD), subgingival bacteria initiate and sustain a non-resolving inflammation that is ineffective at controlling the infection. T cells are critical for proper control of infection, but also homeostasis at mucosal surfaces including that of the periodontium. We have previously demonstrated that PD is associated with the local expression of cytokines associated with induction of Th(c)1/Th(c)17 plasticity, whereby loss of oral epithelial cell (OEC) MyD88-dependent-signaling results in exacerbation of this response. The objective of this study was to determine in which T-cell compartment plasticity occurs during PD and whether MyD88-dependent OEC signaling regulates this plasticity. Mice with MyD88-sufficient (B6) or MyD88-deficient (B6OEC.MyD88) OEC were subjected to oral polymicrobial infection for six weeks, after which the severity of disease as measured by alveolar bone loss and immunophenotype of the cellular infiltrate were evaluated. A temporal reduction in the frequency of Th(c)17 cells along with an increased frequency of Th(c)1 and Th(c)1/Th(c)7 cells was observed in B6 mice as PD progressed. This conversion was concomitant with a decrease in the frequency of regulatory T-cells and soft tissue IL10 and TGFβ expression. This immunophenotype was exacerbated in time of onset and magnitude in B6OEC.MyD88mice and was associated with an increase in alveolar bone loss. Together these data demonstrate that T-cell plasticity plays a role in PD whereby OEC-MyD88-signaling at least in part controls this plasticity. These data suggest that OECs can be a target for local modulation of T-cell plasticity as an intervention for the treatment of periodontal disease.