Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Discipline of Medical Gerontology, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.
JCI Insight. 2022 Sep 22;7(18):e135407. doi: 10.1172/jci.insight.135407.
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.
虽然已发表的研究表明 IFN-ε 在调节小鼠生殖道的保护性免疫方面起着关键作用，但据我们所知，IFN-ε 在人女性生殖道 (hFRT) 中的表达和调控尚未得到描述。我们从一个经过充分特征描述的女性队列中获得了 hFRT 样本，使我们能够全面评估月经周期各阶段 hFRT 中 IFN-ε 的体外表达情况。我们发现，在各种类型的 IFNs 中，IFN-ε 仅在 hFRT 上皮细胞中特异性且组成性地表达。与下 hFRT 的复层鳞状上皮的基底层相比，它在上 hFRT 的表面和腺上皮中具有独特的表达模式。在上 hFRT 的子宫内膜上皮中存在 IFN-ε 表达的周期性变化，而在下 hFRT 的远端 FRT 中则没有，这与孕激素受体在上 hFRT 的选择性子宫内膜表达和孕激素对 IFNE 启动子的调节一致。因为我们表明 IFN-ε 刺激了 FRT 上皮中的重要保护性 IFN 调节基因，所以这种特征是理解激素对黏膜免疫控制机制的关键要素。
