Fine-tuning of Th17 Cytokines in Periodontal Disease by IL-10

Abstract

Periodontitis (PD) is a chronic disease caused by the host inflammatory response to bacteria colonizing the oral cavity. In addition to tolerance to oral microbiome, a fine-tuned balance of IL-10 levels is critical to efficiently mount antimicrobial resistance without causing immunopathology. Clinical and animal studies support that adaptive T-helper (Th) cytokines are involved in the pathogenesis of alveolar bone destruction in PD. However, it remains unclear what type of Th response is related to human PD progression and what role IL-10 has on this process. We addressed the contribution of IL-10 in limiting Th1 and Th17 inflammatory response in murine and human PD. Through a combination of basic and translational approaches involving selected cytokine-deficient mice as well as human genetic epidemiology, our results demonstrate the requirement for IL-10 in fine-tuning the levels of Th17 (IL-17A and IL-17F) cytokines in experimental and human PD. Of novelty, we found that IL-17F correlated with protection in murine and human PD and was positively regulated by IL-10. To our knowledge, this is the first demonstration of the protective role for IL-17F in PD, its positive regulation by IL-10, and the potential differential role for IL-17A and IL-17F in periodontal disease.

Nanomaterials for Tissue Engineering In Dentistry

“…For example, growth factors and biological studies for periodontal regeneration have included bone morphogenetic proteins 2, 3, 4, 6, 7, 12; cell-binding peptide p-15; fibroblast growth factor-2; growth differentiation factor −5; insulin-like growth factor-1; matrix factors (fibronectin, amelogenins, thrombospondin); platelet-derived growth factor; platelet-rich plasma; vascular endothelial growth factor; and enamel matrix derivative [76,77,78]. In the case of pulpodentin complex, inductive growth may come from the regeneration of degraded dentin matrix [79], from revitalization process or synthesized in vitro and delivered into tissues [80].…”

Treg regulation in periodontal disease during pregnancy.

“…Recently, IL-10 has also been known to contribute to regulating Th17 cytokines in periodontal disease. IL-10 regulation of IL-17 was associated with reduced periodontal tissue inflammation and bone resorption (Moretti et al, 2015). Observed increase of IL-17 expression in gingival tissue during pregnancy may be attributed to downregulation of IL-10 expression.…”

“…Treg cells attenuate inflammation and bone resorption and express antiinflammatory cytokine Il-10 which has been proposed to regulate Il-17 expression in periodontal disease (Gustavo P. Moretti et al, 2015).…”

“…Expression of Treg related cytokines such as TGFβ and Il-10 have been linked to suppressing Th1 and Th17 cell development (Gorelik, Constant, & Flavell, 2002;Li, Wan, & Flavell;Moretti et al, 2015). We therefore investigated gingival expression of Treg related molecules in pregnant and non-pregnant mice.…”

“…Expression of TGFβ can promote Treg differentiation by inducing FoxP3 gene expression (W. Chen et al, 2003) as well as suppress the development of Th1 and Th17 cells Zhou et al, 2008). Similarly, Treg IL-10 signaling suppresses development of Th17 (Huber et al, 2011) and attenuates tissue damage and bone resorption in periodontal disease (Moretti et al, 2015). In infection induced pregnant mice, we detected decreased expression of both TGFβ and IL-10 compared to non-pregnant mice ( Figure 4A).…”