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.

RORγt+Foxp3+ Cells are an Independent Bifunctional Regulatory T Cell Lineage and Mediate Crescentic GN

“…7,8 Multiple studies by several independent groups could also show the presence of IL-17 secreting biTregs in patients with different inflammatory pathologies including ulcerative colitis, 9 colonic cancer, 10 psoriasis, 11 peridontitis, 12 and juvenile arthritis. 13 While all these studies reported an association of biTregs with inflammation and tumors, their functional role remains widely unknown.…”

Maturation of the Host Response and its Impact upon Periodontal Disease

“…An animal study supports the role of IL-17 and Th17 in gingival inflammation and subsequent destruction of alveolar bone in periodontitis [9]. There is also evidence of the presence of IL-17 and Th17 cells in human periodontal lesions which may be associated with increasing disease severity [10].…”

Evaluation of the expression of T helper lymphocytes markers associated with Th1, Th2, Th17, and Treg cells in primary pterygium biopsies

“…En estudios realizados previamente en pacientes con Pt primario y recidivante, se encontró que ambos mostraban un nivel elevado de IL-17 en la película lagrimal, por lo que se sugiere que podría estar asociado con su causa y recurrencia 21 . Las células Th IL-17 + Foxp3 + han sido identificadas en diversas enfermedades humanas, como la enfermedad inflamatoria intestinal 22 , tumores de colon 23 , periodontitis 24 , psoriasis 25 y artritis reumatoide 26 . Característicamente estas células conservan la actividad inmunosupresora de los linfocitos Treg, al tiempo que adquieren capacidad efectora por la producción de IL-17 20 .…”