Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/8582
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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