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Title: | Early growth response gene 2 (Egr-2) controls the self-tolerance of T cells and prevents the development of lupuslike autoimmune disease |
Authors: | Symonds, ALJ Martin, JE Kioussis, D Wraith, DC Li, S Wang, P |
Keywords: | T cells;Early growth response gene 2;Autoimmune disease;Antigens |
Issue Date: | 2008 |
Publisher: | The Rockefeller University Press |
Citation: | Journal of Experimental Medicine, 205(10), 2295 - 2307, 2008 |
Abstract: | Maintaining tolerance of T cells to self-antigens is essential to avoid autoimmune disease. How self-reactive T cells are kept functionally inactive is, however, unknown. In this study, we show that early growth response gene 2 (Egr-2), a zinc-finger transcription factor, is expressed in CD44(high) T cells and controls their proliferation and activation. In the absence of Egr-2, CD44(high), but not CD44(low) T cells, are hyperreactive and hyperproliferative in vivo. The accumulation of activated CD4(+)CD44(high) T cells leads to the development of a late onset lupuslike autoimmune disease characterized by the accumulation of interferon (IFN)-gamma and interleukin (IL)-17-producing CD4(+) T cells, loss of tolerance to nuclear antigens, massive infiltration of T cells into multiple organs and glomerulonephritis. We found that the expression of cyclin-dependent kinase inhibitor p21cip1 was impaired in Egr-2-deficient T cells, whereas the expression of IFN-gamma and IL-17 in response to T cell receptor ligation was significantly increased, suggesting that Egr-2 activates the expression of genes involved in the negative regulation of T cell proliferation and inflammation. These results demonstrate that Egr-2 is an intrinsic regulator of effector T cells and controls the expansion of self-reactive T cells and development of autoimmune disease. |
Description: | © 2008 Zhu et al. This article is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
URI: | http://jem.rupress.org/content/205/10/2295 http://bura.brunel.ac.uk/handle/2438/8582 |
DOI: | http://dx.doi.org/10.1084/jem.20080187 |
ISSN: | 0022-1007 |
Appears in Collections: | Biological Sciences Publications Dept of Life Sciences Research Papers |
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