Aim: T lymphocytes play a central role during the pathogenesis of periodontitis, and the imbalance between the pathogenic T-helper type 17 (Th17) and protective T-regulatory (Treg) lymphocytes determines the tooth-supporting alveolar bone resorption. Interleukin (IL)-35 is a novel anti-inflammatory cytokine with therapeutic properties in diseases whose pathogenesis is associated with the Th17/Treg imbalance; however, its role during periodontitis has not been established yet. This study aimed to elucidate whether IL-35 inhibits the alveolar bone resorption during periodontitis by modulating the Th17/Treg imbalance. Materials and Methods: Mice with ligature-induced periodontitis were treated with locally or systemically administrated IL-35. As controls, periodontitis-affected mice without IL-35 treatment and non-ligated mice were used. Alveolar bone resorption was measured by micro-computed tomography and scanning electron microscopy. The Th17/Treg pattern of the immune response was analysed by qPCR, ELISA, and flow cytometry. Results: IL-35 inhibited alveolar bone resorption in periodontitis mice. Besides, IL-35 induced less detection of Th17 lymphocytes and production of Th17-related cytokines, together with higher detection of Treg lymphocytes and production of Tregrelated cytokines in periodontitis-affected tissues. Conclusion: IL-35 is beneficial in the regulation of periodontitis; particularly, IL-35 inhibited alveolar bone resorption and this inhibition was closely associated with modulation of the periodontal Th17/Treg imbalance. K E Y W O R D S alveolar bone loss, interleukin-35, periodontitis, RANKL, T lymphocytes | 677 CAFFERATA ET Al.

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Mesenchymal stem cells (MSCs) exhibit potent immunoregulatory abilities by interacting with cells of the adaptive and innate immune system. In vitro, MSCs inhibit the differentiation of T cells into T helper 17 (Th17) cells and repress their proliferation. In vivo, the administration of MSCs to treat various experimental inflammatory and autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and bowel disease showed promising therapeutic results. These therapeutic properties mediated by MSCs are associated with an attenuated immune response characterized by a reduced frequency of Th17 cells and the generation of regulatory T cells. In this manuscript, we review how MSC and Th17 cells interact, communicate, and exchange information through different ways such as cell-to-cell contact, secretion of soluble factors, and organelle transfer. Moreover, we discuss the consequences of this dynamic dialogue between MSC and Th17 well described by their phenotypic and functional plasticity.

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