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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{dagger}

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.

{dagger} 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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