Background: Interleukin (IL)-17 produced by mainly T helper 17 (Th17) cells may play an important destructive role in chronic periodontitis (CP). Thus, anti-inflammatory cytokines, such as IL-35, might have a beneficial effect in periodontitis by inhibiting differentiation of Th17 cells. Th17 differentiation is regulated by the retinoic acid receptor-related orphan receptor (ROR) (encoded by ) and RORt (encoded by ). However, the role of IL-35 in periodontitis is not clear and the effect of IL-35 on the function of Th17 cells is still incompletely understood. Therefore, we investigated the effects of IL-35 on Th17 cells.

Methods: Peripheral blood mononuclear cells (PBMCs) were sampled from three healthy volunteers and three CP patients and were analyzed by flow cytometry for T cell population. Th17 cells differentiated by a cytokine cocktail (recombinant transforming growth factor-, rIL-6, rIL-1, anti-interferon (IFN)-, anti-IL-2 and anti-IL-4) from PBMCs were cultured with or without rIL-35. (which usually refers to IL-17), and mRNA expression was analyzed by quantitative polymerase chain reaction, and IL-17A production was determined by enzyme-linked immunosorbent assay.

Results: The proportion of IL-17ACD4 slightly increased in CP patients compared with healthy controls, however, there were no significant differences in the percentage of IL-17ACD4 as well as IFN-CD4 and Foxp3CD4 T cells between healthy controls and CP patients. , and mRNA expression was significantly increased in Th17 cells induced by the cytokine cocktail, and the induction was significantly inhibited by addition of rIL-35 (1 ng/mL). IL-17A production in Th17 cells was significantly inhibited by rIL-35 addition (1 ng/mL).

Discussion: The present study suggests that IL-35 could directly suppress IL-17 expression via ROR and RORt inhibition and might play an important role in inflammatory diseases such as periodontitis.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314955PMC
http://dx.doi.org/10.7717/peerj.2999DOI Listing

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