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Molecular and Cellular Biology, November 2003, p. 7638-7647, Vol. 23, No. 21
0270-7306/03/$08.00+0 DOI: 10.1128/MCB.23.21.7638-7647.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Egr Family Members Regulate Nonlymphoid Expression of Fas Ligand, TRAIL, and Tumor Necrosis Factor during Immune Responses
Nathalie M. Droin, Michael J. Pinkoski, Emmanuel Dejardin, and Douglas R. Green*
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121
Received 3 April 2003/
Returned for modification 25 April 2003/
Accepted 9 July 2003
The Fas ligand (FasL)/Fas pathway is crucial for homeostasis of the immune system and peripheral tolerance. Peripheral lymphocyte deletion involves FasL/Fas in at least two ways: coexpression of both Fas and its ligand on T cells, leading to activation-induced cell death, and expression of FasL by nonlymphoid cells, such as intestinal epithelial cells (IEC), that kill Fas-positive T cells. We demonstrate here that superantigen Staphylococcus enterotoxin B (SEB) induced a dramatic upregulation of FasL, TRAIL, and TNF mRNA expression and function in IEC from BALB/c and C57BL/6 mice. Using adoptive transfer in which CD4+ T cells from OT-2 T-cell receptor transgenic mice were transferred into recipients, we observed an induction in IEC of FasL, TRAIL, and TNF mRNA after administration of antigen. Specific Egr-binding sites have been identified in the 5' promoter region of the FasL gene, and Egr-1, Egr-2, and Egr-3 mRNA in IEC from mice treated with SEB and from transgenic OT-2 mice after administration of antigen was upregulated. Overexpression of Egr-2 and Egr-3 induced endogenous ligand upregulation that was inhibited by overexpression of Egr-specific inhibitor Nab1. These results support a role for Egr family members in nonlymphoid expression of FasL, TRAIL, and TNF.
* Corresponding author. Mailing address: La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121. Phone: (858) 558-4675. Fax: (858) 558-3526. E-mail: Dgreen5240{at}aol.com.
La Jolla Institute for Allergy and Immunology article no. 559.
Molecular and Cellular Biology, November 2003, p. 7638-7647, Vol. 23, No. 21
0022-538X/03/$08.00+0 DOI: 10.1128/MCB.23.21.7638-7647.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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