{"doi":"10.7717/peerj.2999","title":"Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4<sup>+</sup> T cells","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>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)<jats:italic>α</jats:italic>(encoded by<jats:italic>RORA</jats:italic>) and ROR<jats:italic>γ</jats:italic>t (encoded by<jats:italic>RORC</jats:italic>). 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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-<jats:italic>β</jats:italic>, rIL-6, rIL-1<jats:italic>β</jats:italic>, anti-interferon (IFN)-<jats:italic>γ</jats:italic>, anti-IL-2 and anti-IL-4) from PBMCs were cultured with or without rIL-35.<jats:italic>IL17A</jats:italic>(which usually refers to IL-17),<jats:italic>RORA</jats:italic>and<jats:italic>RORC</jats:italic>mRNA expression was analyzed by quantitative polymerase chain reaction, and IL-17A production was determined by enzyme-linked immunosorbent assay.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The proportion of IL-17A<jats:sup>+</jats:sup>CD4<jats:sup>+</jats:sup>slightly increased in CP patients compared with healthy controls, however, there were no significant differences in the percentage of IL-17A<jats:sup>+</jats:sup>CD4<jats:sup>+</jats:sup>as well as IFN-<jats:italic>γ</jats:italic><jats:sup>+</jats:sup>CD4<jats:sup>+</jats:sup>and Foxp3<jats:sup>+</jats:sup>CD4<jats:sup>+</jats:sup>T cells between healthy controls and CP patients.<jats:italic>IL17A</jats:italic>,<jats:italic>RORA</jats:italic>and<jats:italic>RORC</jats:italic>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).</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>The present study suggests that IL-35 could directly suppress IL-17 expression via ROR<jats:italic>α</jats:italic>and ROR<jats:italic>γ</jats:italic>t inhibition and might play an important role in inflammatory diseases such as periodontitis.</jats:p></jats:sec>","journal":"PeerJ","year":2017,"id":13826,"datarank":1.7043287214588665,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":1.1586907974999086,"self_endowment_contribution":0.5456379239589579,"citer_contribution":1.1586907974999086,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":31,"citers_with_citation_signal":30,"citers_with_endowment":30,"datacite_reuse_total":6,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":111816,"name":"Takeki Fujimura","orcid":null,"position":1,"is_corresponding":false},{"id":111817,"name":"Takeshi 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