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This article is part of the supplement: Proceedings of 18th Pediatric Rheumatology European Society (PReS) Congress

Open Access Poster presentation

Overexpression of CREMαlpha accelerates onset and severity of auto-immune mediated disease in a murine model of lupus

Kim Ohl1*, Ralph Lippe2, Eva Verjans1, Nora Honke1, Karin Maschke-Neuss1, Norbert Wagner1, Johannes Roth2 and Klaus Tenbrock1

Author Affiliations

1 Klinik für Kinder und Jugendmedizin, Klinikum der RWTH Aachen

2 Institut für Immunologie, Universität Münster

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Pediatric Rheumatology 2011, 9(Suppl 1):P289  doi:10.1186/1546-0096-9-S1-P289


The electronic version of this article is the complete one and can be found online at: http://www.ped-rheum.com/content/9/S1/P289


Published:14 September 2011

© 2011 Ohl et al; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Poster presentation

The transcription factor cAMP response element modulator (CREM) is a widely expressed transcriptional repressor which is important for the termination of the T cell immune response. CREMα is overexpressed in SLE (Systemic lupus erythematosus) T cells and is supposed to be a key player in orchestrating the transcriptional program of SLE T cells by targeting T cell-relevant genes. To explore the relevance of CREMα in vivo we used a well-established murine lupus model, which is characterized by the introduction of a mutation in the CD95 (Fas) locus. We generated a transgenic mouse with a selective overexpression of CREMα in T cells and introduced a Fas -/- phenotype into the CREMα transgenic mice. CREMα transgenic Fas -/- mice developed a severe lymphadenopathy and splenomegaly as early as 8 weeks of age, while the wildytpe Fas -/- mice did not at this early age. Lymphadenopathy and splenomegaly is paralleled by a massive expansion of pathogenic CD3+CD4-CD8- double negative T cells. Furthermore T cells of CREMα transgenic Fas -/- mice show an enhanced production of IL-21 and IL-17, which are hallmark cytokines of highly inflammatory Th17 cells. Vice versa percentages of regulatory T cells are reduced. The enhanced occurrence of aberrant and inflammatory T cells further leads to increased B cell activation, increased anti-DNA antibody titers and finally shortened life expectation of these mice.

Our experiments are the proof of principle for a critical amplifying role of CREMα in autoimmune prone conditions like SLE.