Expression of Interferon Epsilon in Mucosal Epithelium is Regulated by Elf3

Abstract

Interferon epsilon (IFNε) is a unique type I interferon (IFN) that shows distinct constitutive expression in reproductive tract epithelium. Understanding how IFNε expression is regulated is critical for the mechanism of action in protecting the mucosa from infection. Combined computational and experimental investigation of the promoter of IFNε predicted transcription factor binding sites for the ETS family of transcription factors. We demonstrate here that Ifnε is regulated by Elf3, an epithelial restricted member of the ETS family. It is co-expressed with IFNε at the epithelium of uterus, lung and intestine, and we focused on regulation of IFNε expression in the uterus. Promoter reporter studies demonstrated that Elf3 was a strong driver of Ifnε expression; knockdown of Elf3 reduced expression levels of IFNε; Elf3 regulated Ifnε expression and chromatin immunoprecipitation (ChIP) confirmed the direct binding of Elf3 to the IFNε promoter. These data show that Elf3 is important in regulating protective mucosal immunity by driving constitutive expression of IFNε to protect mucosal tissues from infection in at least three organ systems.

Keywords:

• IFNε
• Elf3
• regulation

Acknowledgments

The authors acknowledge the facilities and scientific and technical assistance of the Monash Histology Platform, Department of Anatomy and Developmental Biology, Monash University. EDG and PJH were funded by NHMRC.

Disclosure statement

No potential conflict of interest was reported by the author.

Additional information

Funding

This work was supported by National Health and Medical Research Council; National Health and Medical Research Council.