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

Open Access Open Badges Oral 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, Germany

2 Institut für Immunologie, Universität Münster, Germany

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Pediatric Rheumatology 2011, 9(Suppl 1):O3  doi:10.1186/1546-0096-9-S1-O3

The electronic version of this article is the complete one and can be found online at:

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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Oral 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.