Affiliation:
1. Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121
Abstract
ABSTRACT
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
.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
59 articles.
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