A novel cytokine consisting of the p40 and EBI3 subunits suppresses experimental autoimmune arthritis via reciprocal regulation of Th17 and Treg cells

查看全文 作　　者：Seon-Yeong [1,5]Lee;Su-Jin [2,5]Moon;Young-Mee [1,5]Moon;Hyeon-Beom [1]Seo;Jun-Geol [1]Ryu;A Ram [1,3]Lee;Chae Rim [1,3]Lee;Da-Som [1]Kim;Yang-Mi [1]Her;Jeong Won [1]Choi;Seung-Ki [2]Kwok;Sung-Hwan [2]Park;Mi-La [1,4]Cho

机构地区：[1]The Rheumatism Research Center,The Catholic University of Korea,Seoul,South Korea;[2]Division of Rheumatology,Department of Internal Medicine,Seoul St.Mary’s Hospital,College of Medicine,The Catholic University of Korea,Seoul,South Korea;[3]Department of Biomedicine&Health Sciences,College of Medicine,The Catholic University of Korea,Seoul,South Korea;[4]Department of Medical Lifescience,College of Medicine,The Catholic University of Korea,Seoul,South Korea;[5]These author contributed equally:Seon-Yeong Lee,Su-Jin Moon,Young-Mee Moon

出　　处：《Cellular & Molecular Immunology》索引2022年第19卷第1期,共13页

基　　金：This work was supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(NRF-2017R1A2B3007688);a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HI20C1496);the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2021R1I1A1A01056024). 摘　　要：OBJECTIVE:The interleukin(IL)-12 cytokine family is closely related to the development of T helper cells,which are responsible for autoimmune disease enhancement or suppression.IL-12 family members are generally heterodimers and share threeα-subunits(p35,p19,and p28)and twoβ-subunits(p40 and EBI3).However,aβ-sheet p40 homodimer has been shown to exist and antagonize IL-12 and IL-23 signaling 1.Therefore,we assumed the existence of a p40-EBI3 heterodimer in nature and sought to investigate its role in immune regulation.METHODS:The presence of the p40-EBI3 heterodimer was confirmed by ELISA,immunoprecipitation,and western blotting.A p40-EBI3 vector and p40-EBI3-Fc protein were synthesized to confirm the immunological role of this protein in mice with collageninduced arthritis(CIA).The anti-inflammatory effects of p40-EBI3 were analyzed with regard to clinical,histological,and immune cell-regulating features in mice with CIA.RESULTS:Clinical arthritis scores and the expression levels of proinflammatory cytokines(e.g.,IL-17,IL-1β,IL-6,and TNF-α)were significantly attenuated in p40-EBI3-overexpressing and p40-EBI3-Fc-treated mice with CIA compared to vehicle-treated mice with CIA.Structural joint damage and vessel formation-related gene expression were also reduced by p40-EBI3 heterodimer treatment.In vitro,the p40-EBI3-Fc protein significantly suppressed the differentiation of Th17 cells and reciprocally induced CD4+CD25+Foxp3+(regulatory T)cells.p40-EBI3 also inhibited osteoclast formation in a concentrationdependent manner.CONCLUSION:In this study,p40-EBI3 ameliorated proinflammatory conditions both in vivo and in vitro.We propose that p40-EBI3 is a novel anti-inflammatory cytokine involved in suppressing the immune response through the expansion of Treg cells and suppression of Th17 cells and osteoclastogenesis. 关键词：CYTOKINE p40-EBI3 Rheumatoid arthritis Autoimmune disease regulatory T cell

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A novel cytokine consisting of the p40 and EBI3 subunits suppresses experimental autoimmune arthritis via reciprocal regulation of Th17 and Treg cells

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