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The transcription factor CREM drives an inflammatory phenotype of T cells in oligoarticular juvenile idiopathic arthritis

Ohl, K; Nickel, H; Moncrieffe, H; Klemm, P; Scheufen, A; Foell, D; Wixler, V; ... Tenbrock, K; + view all (2018) The transcription factor CREM drives an inflammatory phenotype of T cells in oligoarticular juvenile idiopathic arthritis. Pediatric Rheumatology , 16 , Article 39. 10.1186/s12969-018-0253-x. Green open access

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Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: In conclusion, our study reveals that beyond its role in SLE T cells CREM also drives an inflammatory phenotype of T cells in JIA.

Type: Article
Title: The transcription factor CREM drives an inflammatory phenotype of T cells in oligoarticular juvenile idiopathic arthritis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12969-018-0253-x
Publisher version: https://doi.org/10.1186/s12969-018-0253-x
Language: English
Additional information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Science & Technology, Life Sciences & Biomedicine, Pediatrics, Rheumatology, CREM, JIA, Effector T Cells, Systemic-Lupus-Erythematosus, Responsive Element Modulator, Suppresses IL-2 Production, Alpha, Overexpression, Autoimmunity, Activation, Expression, Expansion, Promoter
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10053281
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