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7.1 Transgenic overexpression of CREM alpha in murine T cells results in an anergic phenotype with enhanced IL17 production

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Background and methods

The cAMP responsive element modulator CREMa is a transcriptional repressor and putatively important in T cell pathophysiology of Systemic Lupus Erythematosus (SLE). To clarify the relevance of CREMa we overexpressed CREMa under control of the T cell specific CD2 promoter in mice.

Results

As expected, overall T cell proliferation in naive T cells as response to different stimuli like anti-CD3 or an allogenic MLR was diminished in CREMa transgenic mice compared to wildtype mice, however-unexpectedly – disease activity in a contact dermatitis model was more severe in transgenic mice. Moreover, when T cells purified from the lymphnodes of the challenged ears were used for proliferation assays, transgenic T cell showed an enhanced proliferative response. Additionally, T cells from transgenic mice displayed an enhanced IL-17 production.

Conclusion

These data suggest that murine T cells with a transgenic overexpression of CREMa show an anergic phenotype in vitro, however when challenged in an in vivo disease model they react in a way, which predisposes to autoimmunity. Thus these T cells partially mimic the phenotype of human SLE T cells and support the relevance of CREMa for the pathophysiology of SLE.

Author information

Correspondence to RL Lippe.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Lippe, R., Sturm, K., Roth, J. et al. 7.1 Transgenic overexpression of CREM alpha in murine T cells results in an anergic phenotype with enhanced IL17 production. Pediatr Rheumatol 6, S11 (2008) doi:10.1186/1546-0096-6-S1-S11

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Keywords

  • Systemic Lupus Erythematosus
  • Transgenic Mouse
  • Dermatitis
  • Transcriptional Repressor
  • Contact Dermatitis