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J Neuroimmunol. 2012 Sep 15;250(1-2):35-43. doi: 10.1016/j.jneuroim.2012.05.012. Epub 2012 Jun 10.

Sustained Rap1 activation in autoantigen-specific T lymphocytes attenuates experimental autoimmune encephalomyelitis.

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  • 1Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.


Altered Ras superfamily guanine nucleotide triphosphatase signaling may contribute to the activation of autoreactive T cells in diseases such as rheumatoid arthritis and systemic lupus erythematosus. Here, we show that transgenic expression of activated Rap1, a Ras-related protein which is protective in murine arthritis, in both wildtype (WT) and 2D2 mice, enhances autoreactive T cell activation by myelin oligodendrocyte glycoprotein peptide in vitro and in vivo. However, RapV12 reduces the number of autoreactive T cells in both WT and 2D2 mice, and increases murine survival in experimental autoimmune encephalitis, suggesting Rap1 activation restricts autoimmune T cell-mediated pathology through enhancing tolerance.

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