Please use this identifier to cite or link to this item:
http://bura.brunel.ac.uk/handle/2438/8582
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Symonds, ALJ | - |
dc.contributor.author | Martin, JE | - |
dc.contributor.author | Kioussis, D | - |
dc.contributor.author | Wraith, DC | - |
dc.contributor.author | Li, S | - |
dc.contributor.author | Wang, P | - |
dc.date.accessioned | 2014-06-20T13:37:56Z | - |
dc.date.available | 2014-06-20T13:37:56Z | - |
dc.date.issued | 2008 | - |
dc.identifier.citation | Journal of Experimental Medicine, 205(10), 2295 - 2307, 2008 | en_US |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | http://jem.rupress.org/content/205/10/2295 | en |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/8582 | - |
dc.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/). | en_US |
dc.description.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. | en_US |
dc.description.sponsorship | The Biotechnology and Biological Sciences Research Council, the Medical Research Council and the Wellcome Trust. | en_US |
dc.language | eng | - |
dc.language.iso | en | en_US |
dc.publisher | The Rockefeller University Press | en_US |
dc.subject | T cells | en_US |
dc.subject | Early growth response gene 2 | en_US |
dc.subject | Autoimmune disease | en_US |
dc.subject | Antigens | en_US |
dc.title | Early growth response gene 2 (Egr-2) controls the self-tolerance of T cells and prevents the development of lupuslike autoimmune disease | en_US |
dc.type | Article | en_US |
dc.identifier.doi | http://dx.doi.org/10.1084/jem.20080187 | - |
pubs.organisational-data | /Brunel | - |
pubs.organisational-data | /Brunel/Brunel Active Staff | - |
pubs.organisational-data | /Brunel/Brunel Active Staff/School of Health Sciences & Social Care | - |
pubs.organisational-data | /Brunel/Brunel Active Staff/School of Health Sciences & Social Care/Biological Sciences | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups/Brunel Institute of Cancer Genetics and Pharmacogenomics | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups/Centre for Systems and Synthetic Biology | - |
Appears in Collections: | Biological Sciences Publications Dept of Life Sciences Research Papers |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Fulltext.pdf | 2.93 MB | Adobe PDF | View/Open |
Items in BURA are protected by copyright, with all rights reserved, unless otherwise indicated.