PMID- 18779345
OWN - NLM
STAT- MEDLINE
DCOM- 20081014
LR  - 20220129
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 205
IP  - 10
DP  - 2008 Sep 29
TI  - Early growth response gene 2 (Egr-2) controls the self-tolerance of T cells and 
      prevents the development of lupuslike autoimmune disease.
PG  - 2295-307
LID - 10.1084/jem.20080187 [doi]
AB  - 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.
FAU - Zhu, Bo
AU  - Zhu B
AD  - Institute of Cell and Molecular Science, Barts and London School of Medicine and 
      Dentistry, University of London, London E1 2AT, England, UK.
FAU - Symonds, Alistair L J
AU  - Symonds AL
FAU - Martin, Joanne E
AU  - Martin JE
FAU - Kioussis, Dimitris
AU  - Kioussis D
FAU - Wraith, David C
AU  - Wraith DC
FAU - Li, Suling
AU  - Li S
FAU - Wang, Ping
AU  - Wang P
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 074731/WT_/Wellcome Trust/United Kingdom
GR  - MC_U117512796/MRC_/Medical Research Council/United Kingdom
GR  - BB_/Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080908
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Autoantibodies)
RN  - 0 (Cdkn1a protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (Egr2 protein, mouse)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Interleukin-2)
SB  - IM
MH  - Animals
MH  - Autoantibodies/immunology
MH  - *Autoimmune Diseases/genetics/immunology/pathology
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cyclin-Dependent Kinase Inhibitor p21/genetics/immunology
MH  - Early Growth Response Protein 2/genetics/*immunology
MH  - Hyaluronan Receptors/immunology
MH  - Interleukin-2/immunology
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - *Self Tolerance/genetics/immunology
MH  - Skin/pathology
MH  - Spleen/anatomy & histology/immunology
MH  - T-Lymphocyte Subsets/immunology/*physiology
MH  - T-Lymphocytes/immunology/*physiology
PMC - PMC2556781
EDAT- 2008/09/10 09:00
MHDA- 2008/10/15 09:00
PMCR- 2009/03/29
CRDT- 2008/09/10 09:00
PHST- 2008/09/10 09:00 [pubmed]
PHST- 2008/10/15 09:00 [medline]
PHST- 2008/09/10 09:00 [entrez]
PHST- 2009/03/29 00:00 [pmc-release]
AID - jem.20080187 [pii]
AID - 20080187 [pii]
AID - 10.1084/jem.20080187 [doi]
PST - ppublish
SO  - J Exp Med. 2008 Sep 29;205(10):2295-307. doi: 10.1084/jem.20080187. Epub 2008 Sep 
      8.