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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.
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Research Article Immunology Reproductive biology

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

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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

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Figure 6

IFN-ε protein is expressed in CVL.

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IFN-ε protein is expressed in CVL.
(A) Concentrations of IFN-ε, IL-15, a...
(A) Concentrations of IFN-ε, IL-15, and IL-6 were quantified in CVL fluid (n = 32) using either laboratory-developed (IFN-ε) or commercially available (IL-15, IL-6) immunoassays. There was undetectable cytokine expression in 4 samples for IFN-ε and 2 samples for IL-15. (B) CVL IFN-ε, IL-15, and IL-6 expression was stratified by cycle stage into follicular stage samples (n = 16) and luteal stage samples (n = 16). There was undetectable cytokine expression for IFN-ε in 1 follicular and 3 luteal stage samples and IL-15 in 1 follicular and 1 luteal stage sample. (C) IFNE, IL15, and IL6 mRNA expression, as determined by qPCR, in endometrial, ectocervical, and vaginal biopsy samples stratified into follicular (n = 16) and luteal (n = 16) stages of menstrual cycle. Mann-Whitney U tests were applied to determine cyclic differences for each gene or protein of interest. *P < 0.05, **P < 0.01,***P < 0.001.

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