Oral Administration of All‐Trans Retinoic Acid Suppresses Experimental Periodontitis by Modulating the Th17/Treg Imbalance

Abstract

A T-helper 17 (Th17)/regulatory T (Treg) imbalance has been suggested recently to play a role in the development of periodontitis. All-trans retinoic acid (ATRA) has been reported to modulate Th17/Treg imbalances in some diseases. However, the effect of ATRA on periodontitis remains unknown. This study observes the effect of ATRA on Th17/Treg imbalance modulation in experimental periodontitis. Experimental periodontitis was induced in mice by oral infection with Porphyromonas gingivalis (P. gingivalis). ATRA was orally administered every other day. Alveolar bone resorption (ABR) was estimated by measuring the distance from the cemento-enamel junction to the alveolar bone crest. CD4(+) T-cell subsets in the cervical lymph nodes (CLNs) and spleen were analyzed by flow cytometry. Th17/Treg cell-related cytokine messenger ribonucleic acid expression was quantified by real-time reverse transcription-polymerase chain reaction. The present data shows that ATRA suppressed ABR and inhibited inflammatory cell infiltration into periodontal tissues. These effects were closely associated with reduced CD4(+) retinoid-related orphan receptor γτ(+) cells and increased CD4(+) forkhead box P3(+) cells in the CLNs. Furthermore, ATRA downregulated interleukin (IL)-17A expression and upregulated IL-10 and transforming growth factor-β1 expression in both the CLNs and P. gingivalis-infected gingival tissues. These results suggest that ATRA modulation of the Th17/Treg imbalance provides protection against periodontitis by enhancing Treg cell activation and inhibiting Th17 cell activation. These results indicate the potential for clinical prevention of periodontitis.