The transcription factor CREM drives an inflammatory phenotype of T cells in oligoarticular juvenile idiopathic arthritis.
The transcription factor CREM drives an inflammatory phenotype of T cells in oligoarticular juvenile idiopathic arthritis.
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DOI：
10.1186/s12969-018-0253-x
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发表时间：
2018-06-20
期刊：
影响因子：
--
通讯作者：
Tenbrock K
中科院分区：
文献类型：
--
作者：
Ohl K;Nickel H;Moncrieffe H;Klemm P;Scheufen A;Föll D;Wixler V;Schippers A;Wagner N;Wedderburn LR;Tenbrock K
尽管患有幼年特发性关节炎（JIA）的患者滑膜关节中的Treg细胞数量增加，但炎症效应T细胞仍会引发炎症。cAMP反应元件(CREM)α在SLE、结肠炎和EAE的T细胞调控中起主要作用。然而，其在炎性关节内调节效应T细胞中的作用尚不清楚。流式细胞术分析少关节JIA患者滑液细胞中CREM的表达。外周血单个核细胞与滑液孵育，并使用siRNA实验分析T细胞表型在CREM存在和不存在的情况下。为了验证CREM在体内的作用，我们进行了卵清蛋白诱导的T细胞依赖性关节炎实验。CREM在滑液T细胞中高度表达，用滑液治疗健康对照PBMCs可诱导其表达。具体来说，CREM在T细胞的CD161+亚群中比CD161−亚群中更丰富，并有助于这些细胞的细胞因子表达。最后，通过过继转移CREM - / - T细胞，改善了卵清蛋白诱导的实验性关节炎的发展。总之，我们的研究表明，除了在SLE T细胞中的作用外，CREM还驱动JIA中T细胞的炎症表型。
Inflammatory effector T cells trigger inflammation despite increased numbers of Treg cells in the synovial joint of patients suffering from juvenile idiopathic arthritis (JIA). The cAMP response element (CREM)α is known to play a major role in regulation of T cells in SLE, colitis, and EAE. However, its role in regulation of effector T cells within the inflammatory joint is unknown. CREM expression was analyzed in synovial fluid cells from oligoarticular JIA patients by flow cytometry. Peripheral blood mononuclear cells were incubated with synovial fluid and analyzed in the presence and absence of CREM using siRNA experiments for T cell phenotypes. To validate the role of CREM in vivo, ovalbumin-induced T cell dependent arthritis experiments were performed. CREM is highly expressed in synovial fluid T cells and its expression can be induced by treating healthy control PBMCs with synovial fluid. Specifically, CREM is more abundant in CD161+ subsets, than CD161− subsets, of T cells and contributes to cytokine expression by these cells. Finally, development of ovalbumin-induced experimental arthritis is ameliorated in mice with adoptively transferred CREM−/− T cells. In conclusion, our study reveals that beyond its role in SLE T cells CREM also drives an inflammatory phenotype of T cells in JIA.
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影响因子：
7.3
作者：
Duurland CL;Brown CC;O'Shaughnessy RF;Wedderburn LR
通讯作者：
Wedderburn LR
影响因子：
--
作者：
Hinks, Anne;Ke, Xiayi;Barton, Anne;Eyre, Steve;Bowes, John;Worthington, Jane;Thompson, Susan D.;Langefeld, Carl D.;Glass, David N.;Thomson, Wendy
通讯作者：
Thomson, Wendy
人白细胞介素17产生的细胞起源于CD161+ CD4+ T细胞前体。
影响因子：
15.3
作者：
Cosmi, Lorenzo;De Palma, Raffaele;Santarlasci, Veronica;Maggi, Laura;Capone, Manuela;Frosali, Francesca;Rodolico, Gabriella;Querci, Valentina;Abbate, Gianfranco;Angeli, Roberta;Berrino, Liberato;Fambrini, Massimiliano;Caproni, Marzia;Tonelli, Francesco;Lazzeri, Elena;Parronchi, Paola;Liotta, Francesco;Maggi, Enrico;Romagnani, Sergio;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
影响因子：
32.4
作者：
Santarlasci, Veronica;Maggi, Laura;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
影响因子：
--
作者：
Cosmi, Lorenzo;Cimaz, Rolando;Annunziato, Francesco
通讯作者：
Annunziato, Francesco