The Presence of IL-17+/FOXP3+ Double-positive Cells in Periodontitis

Abstract

Increasing evidence suggests that distinct inflammatory cytokines convert forkhead box protein P3 (FOXP3+) regulatory T-cells (Tregs) into IL-17-producing cells (Th17 cells) in vitro. However, this functional plasticity has not been examined in the pathogenesis of periodontal disease. In this study, we analyzed the IL-17A+FOXP3+ cells present in periodontitis lesions to determine the association between Treg conversion and the pathogenesis of periodontitis. The immunohistochemical analysis of gingival tissues demonstrated that the numbers of Th17 cells (IL-17A+FOXP3−) and Tregs (IL-17A−FOXP3+) were greater in periodontitis lesions than in gingivitis lesions. We further identified a small number of IL-17A+FOXP3+ cells in periodontitis lesions but not in gingivitis lesions. The flow cytometry analysis of CD4+ T-cell lines established from gingival tissues and the peripheral blood of periodontitis patients showed that the proportion of Tregs was reduced and the proportion of IL-17A+FOXP3+ cells among all FOXP3+ cells was elevated in gingival tissue T-cell lines relative to the proportions in peripheral blood T-cell lines. Our findings indicate that Treg-Th17 conversion may occur in periodontitis lesions. Further studies addressing the role of Treg conversion during inflammatory responses against periodontopathic bacteria are needed.