{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:55:56Z","timestamp":1791640556075,"version":"4.3.4"},"reference-count":41,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T00:00:00Z","timestamp":1487116800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japanese Society for the Promotion of Science (JSPS) KAKENHI Grant","award":["24593134"],"award-info":[{"award-number":["24593134"]}]},{"name":"Japanese Society for the Promotion of Science (JSPS) KAKENHI Grant","award":["25253104"],"award-info":[{"award-number":["25253104"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"\n Background<\/jats:title>\n \n 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)\n \u03b1<\/jats:italic>\n (encoded by\n RORA<\/jats:italic>\n ) and ROR\n \u03b3<\/jats:italic>\n t (encoded by\n RORC<\/jats:italic>\n ). 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.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n 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-\n \u03b2<\/jats:italic>\n , rIL-6, rIL-1\n \u03b2<\/jats:italic>\n , anti-interferon (IFN)-\n \u03b3<\/jats:italic>\n , anti-IL-2 and anti-IL-4) from PBMCs were cultured with or without rIL-35.\n IL17A<\/jats:italic>\n (which usually refers to IL-17),\n RORA<\/jats:italic>\n and\n RORC<\/jats:italic>\n mRNA expression was analyzed by quantitative polymerase chain reaction, and IL-17A production was determined by enzyme-linked immunosorbent assay.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The proportion of IL-17A\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n slightly increased in CP patients compared with healthy controls, however, there were no significant differences in the percentage of IL-17A\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n as well as IFN-\n \u03b3<\/jats:italic>\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n and Foxp3\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n T cells between healthy controls and CP patients.\n IL17A<\/jats:italic>\n ,\n RORA<\/jats:italic>\n and\n RORC<\/jats:italic>\n 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).\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n The present study suggests that IL-35 could directly suppress IL-17 expression via ROR\n \u03b1<\/jats:italic>\n and ROR\n \u03b3<\/jats:italic>\n t inhibition and might play an important role in inflammatory diseases such as periodontitis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.7717\/peerj.2999","type":"journal-article","created":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T04:23:19Z","timestamp":1487132599000},"page":"e2999","source":"Crossref","is-referenced-by-count":31,"title":["Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4\n +<\/sup>\n \u00a0T cells"],"prefix":"10.7717","volume":"5","author":[{"given":"Kosuke","family":"Okada","sequence":"first","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, 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