Exosomal microRNA‐155‐5p from PDLSCs regulated Th17/Treg balance by targeting sirtuin‐1 in chronic periodontitis

Abstract

The mechanism of local inflammation and systemic injury in chronic periodontitis is complicated, in which and exosomes play an important role. In our study, we found that T helper cell 17 (Th17)/regulatory T cell (Treg) balance is destabilized in the peripheral blood of patients with periodontitis, with upregulated Th17 or downregulated Treg, respectively. Porphyromonas gingivalis lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment of chronic periodontitis. The exosomes were extracted from periodontal ligament stem cells (PDLSCs) in LPSinduced periodontitis environment, which inversely effected on CD4+ T cells under normal and inflammatory conditions. Furthermore, compared with exosomes from normal PDLSCs, lower expression of microRNA-155-5p (miR-155-5p) and higher expression of Sirtuin-1 (SIRT1) were observed in exosomes from LPS-stimulated PDLSCs. Exosomes from PDLSCs alleviated inflammatory microenvironment through Th17/Treg/miR-155-5p/SIRT1 regulatory network. This study aimed to find the "switching" factors that affected the further deterioration of periodontitis to maximally control the multiple downstream damage signal factors to further understand periodontitis and find new targets for its treatment.

PDLSCs Regulate Angiogenesis of Periodontal Ligaments via VEGF Transferred by Exosomes in Periodontitis

“…Therefore, a transwell indirect co-culture system was employed to mimic cell-to-cell communication. Functions of PDLSCs are affected by inflammatory environment resulted from periodontitis, such as proliferative capacity, osteogenic potential and regulatory ability [27][28][29]. In our study, VEGFA, the vascular specific marker, was up-regulated in PDLSCs derived from periodontitis, suggesting that inflammation might affect the pro-angiogenesis of PDLSCs.…”

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

“…cells, downregulation pro-inflammatory IL-17, promotion differentiation of Tregs (31,51,74,76,94) (Table 1) and CTLA-4+ Tregs (74), upregulation anti-inflammatory TGF-β, and inhibition aberrant inflammatory responses in stroke (31), type 1 diabetes (51,76), and chronic periodontitis (94). A possible underlying mechanism could be the immune equilibrium controlled by PGE2 and TGF-β (76) signaling pathways or miRNA-155-5p (94) in EVs. A second underlying mechanism could be the induction of phenotypic transition of macrophages into M2 to regulate T cells indirectly by EVs derived from human NSCs (31) ( Table 1).…”

The Th17/Treg Cell Balance: A Gut Microbiota-Modulated Story

“…Th17 and Treg cells are two vital lymphocyte subsets with opposing functions [11]. Abnormal ratio of Th17 and Treg have been frequently found to be a key feature of metabolic or immunologic disorder-associated diseases, including several types of chronic inflammations [12,13], allergic diseases [14,15], autoimmune diseases, and cancers [16,17]. A number of studies have shown that gut microbiota is closely associated with the balance of Th17 and Treg.…”