Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Spatiotemporal regulation of human IFN-ε and innate immunity in the female reproductive tract
Nollaig M. Bourke, … , Sam Mesiano, Paul J. Hertzog
Nollaig M. Bourke, … , Sam Mesiano, Paul J. Hertzog
Published July 21, 2022
Citation Information: JCI Insight. 2022;7(18):e135407. https://doi.org/10.1172/jci.insight.135407.
View: Text | PDF
Research Article Immunology Reproductive biology

Spatiotemporal regulation of human IFN-ε and innate immunity in the female reproductive tract

  • Text
  • PDF
Abstract

Although published studies have demonstrated that IFN-ε has a crucial role in regulating protective immunity in the mouse female reproductive tract, expression and regulation of IFN-ε in the human female reproductive tract (hFRT) have not been characterized to our knowledge. We obtained hFRT samples from a well-characterized cohort of women to enable us to comprehensively assess ex vivo IFN-ε expression in the hFRT at various stages of the menstrual cycle. We found that among the various types of IFNs, IFN-ε was uniquely, selectively, and constitutively expressed in the hFRT epithelium. It had distinct expression patterns in the surface and glandular epithelia of the upper hFRT compared with basal layers of the stratified squamous epithelia of the lower hFRT. There was cyclical variation of IFN-ε expression in the endometrial epithelium of the upper hFRT and not in the distal FRT, consistent with selective endometrial expression of the progesterone receptor and regulation of the IFNE promoter by progesterone. Because we showed IFN-ε stimulated important protective IFN-regulated genes in FRT epithelium, this characterization is a key element in understanding the mechanisms of hormonal control of mucosal immunity.

Authors

Nollaig M. Bourke, Sharon L. Achilles, Stephanie U-Shane Huang, Helen E. Cumming, San S. Lim, Irene Papageorgiou, Linden J. Gearing, Ross Chapman, Suruchi Thakore, Niamh E. Mangan, Sam Mesiano, Paul J. Hertzog

×

Figure 4

Regulation of IFN-ε by PR.

Options: View larger image (or click on image) Download as PowerPoint
Regulation of IFN-ε by PR.
(A) Negative correlation of both mRNA (left) ...
(A) Negative correlation of both mRNA (left) and protein expression (right) of IFN-ε and PR in hFRT cells. Spearman correlation analysis. (B) Luciferase reporter assay measuring activation of the human IFNE promoter in ECC-1 cells after treatment with either 10 nM progesterone or 10 nM estrogen for 4 hours. Data are from 4 independent biological replicates, each in technical triplicate, shown as mean +SEM and analyzed using Student’s 2-tailed t test. **P < 0.01. (C) Primary uterine epithelial cells were isolated from endometrial biopsy specimens (from up to 6 donors) and cultured for 3 days prior to stimulation for either 1 or 3 hours with 10 nM progesterone or 10 nM estrogen. IFNE expression was quantified using qPCR, expressed relative to expression of 18S and fold change relative to unstimulated control. Significance was determined using Kruskal-Wallis testing with Dunn’s multiple-comparison analysis. *P < 0.05.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts