Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4+ T cells

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 differe...

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Main Authors: Kosuke Okada, Takeki Fujimura, Takeshi Kikuchi, Makoto Aino, Yosuke Kamiya, Ario Izawa, Yuki Iwamura, Hisashi Goto, Iichiro Okabe, Eriko Miyake, Yoshiaki Hasegawa, Makio Mogi, Akio Mitani
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Language:English
Published: PeerJ Inc. 2017-02-01
Series:PeerJ
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Online Access:https://peerj.com/articles/2999.pdf
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author Kosuke Okada
Takeki Fujimura
Takeshi Kikuchi
Makoto Aino
Yosuke Kamiya
Ario Izawa
Yuki Iwamura
Hisashi Goto
Iichiro Okabe
Eriko Miyake
Yoshiaki Hasegawa
Makio Mogi
Akio Mitani
author_facet Kosuke Okada
Takeki Fujimura
Takeshi Kikuchi
Makoto Aino
Yosuke Kamiya
Ario Izawa
Yuki Iwamura
Hisashi Goto
Iichiro Okabe
Eriko Miyake
Yoshiaki Hasegawa
Makio Mogi
Akio Mitani
author_sort Kosuke Okada
collection DOAJ
description 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) α (encoded by RORA) and RORγt (encoded by RORC). 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-β, rIL-6, rIL-1β, anti-interferon (IFN)-γ, anti-IL-2 and anti-IL-4) from PBMCs were cultured with or without rIL-35. IL17A (which usually refers to IL-17), RORA and RORCmRNA expression was analyzed by quantitative polymerase chain reaction, and IL-17A production was determined by enzyme-linked immunosorbent assay. Results The proportion of IL-17A+CD4+ slightly increased in CP patients compared with healthy controls, however, there were no significant differences in the percentage of IL-17A+CD4+ as well as IFN-γ+CD4+ and Foxp3+CD4+ T cells between healthy controls and CP patients. IL17A, RORA and RORC 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 RORα and RORγt inhibition and might play an important role in inflammatory diseases such as periodontitis.
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spelling doaj.art-8bf9dbd466f246b5ae23d93809437ad12023-12-02T21:50:00ZengPeerJ Inc.PeerJ2167-83592017-02-015e299910.7717/peerj.2999Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4+ T cellsKosuke Okada0Takeki Fujimura1Takeshi Kikuchi2Makoto Aino3Yosuke Kamiya4Ario Izawa5Yuki Iwamura6Hisashi Goto7Iichiro Okabe8Eriko Miyake9Yoshiaki Hasegawa10Makio Mogi11Akio Mitani12Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Microbiology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Integrative Education of Pharmacy, School of Pharmacy, Aichi Gakuin University, Nagoya, Aichi, JapanDepartment of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, JapanBackground 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) α (encoded by RORA) and RORγt (encoded by RORC). 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-β, rIL-6, rIL-1β, anti-interferon (IFN)-γ, anti-IL-2 and anti-IL-4) from PBMCs were cultured with or without rIL-35. IL17A (which usually refers to IL-17), RORA and RORCmRNA expression was analyzed by quantitative polymerase chain reaction, and IL-17A production was determined by enzyme-linked immunosorbent assay. Results The proportion of IL-17A+CD4+ slightly increased in CP patients compared with healthy controls, however, there were no significant differences in the percentage of IL-17A+CD4+ as well as IFN-γ+CD4+ and Foxp3+CD4+ T cells between healthy controls and CP patients. IL17A, RORA and RORC 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 RORα and RORγt inhibition and might play an important role in inflammatory diseases such as periodontitis.https://peerj.com/articles/2999.pdfInterleukin-35Interleukin-17PeriodontitisTh17Retinoic acid receptor-related orphan receptor
spellingShingle Kosuke Okada
Takeki Fujimura
Takeshi Kikuchi
Makoto Aino
Yosuke Kamiya
Ario Izawa
Yuki Iwamura
Hisashi Goto
Iichiro Okabe
Eriko Miyake
Yoshiaki Hasegawa
Makio Mogi
Akio Mitani
Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4+ T cells
PeerJ
Interleukin-35
Interleukin-17
Periodontitis
Th17
Retinoic acid receptor-related orphan receptor
title Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4+ T cells
title_full Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4+ T cells
title_fullStr Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4+ T cells
title_full_unstemmed Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4+ T cells
title_short Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4+ T cells
title_sort effect of interleukin il 35 on il 17 expression and production by human cd4 t cells
topic Interleukin-35
Interleukin-17
Periodontitis
Th17
Retinoic acid receptor-related orphan receptor
url https://peerj.com/articles/2999.pdf
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