Dynamic roles of ILC3 in endometrial repair and regeneration

Antonia O. Cuff, Ee Von Woon, Thomas Bainton, Brendan Browne, Phoebe M. Kirkwood, Frances Collins, Douglas A Gibson, Philippa Saunders, Andrew W. Horne, Mark R. Johnson, David A. MacIntyre, Victoria Male
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Abstract

Innate lymphoid cells (ILC) are prominent in the human uterine mucosa and play physiological roles in pregnancy. ILC3 are the second-most common ILC subset in the uterine mucosa, but their role remains unclear. Here we define two subsets of lineage-negative CD56+ CD117+ CRTH2- uterine ILC3, distinguished by their expression of CD127. The CD127- subset is most numerous and active during menstruation and immediately after parturition, suggesting a role in repair of the uterine mucosa (called endometrium outside of pregnancy); the CD127+ subset is most numerous and active immediately after menstruation, as the endometrium regenerates. In healthy endometrium, ILC3 are spatially associated with glandular epithelial and endothelial cells, which both express receptors for the ILC3-derived cytokines, IL-22 and IL-8. In the eutopic endometrium of people with endometriosis, ILC3 are located further from glandular epithelial and endothelial cells suggesting that these cells may be less exposed to ILC3 products, potentially with negative consequences for endometrial regeneration. Our findings highlight the dynamic nature of ILC3 in the uterine mucosa and suggest their primary role is in repair and regeneration. An improved understanding of uterine ILC3 will inform future research on endometrial health and disease.
ILC3 在子宫内膜修复和再生中的动态作用
先天性淋巴细胞(ILC)在人类子宫粘膜中非常突出,在妊娠中发挥着生理作用。ILC3是子宫粘膜中第二常见的ILC亚群,但其作用仍不清楚。在这里,我们定义了两个系阴性 CD56+ CD117+ CRTH2- 子宫 ILC3 亚群,它们通过表达 CD127 来区分。CD127- 亚群在月经期间和分娩后立即出现,数量最多且最活跃,这表明它们在子宫粘膜(妊娠外称为子宫内膜)的修复中发挥作用;CD127+ 亚群在月经后立即出现,数量最多且最活跃,因为子宫内膜正在再生。在健康的子宫内膜中,ILC3 在空间上与腺上皮细胞和内皮细胞相关,而腺上皮细胞和内皮细胞都表达 ILC3 衍生的细胞因子 IL-22 和 IL-8 的受体。在子宫内膜异位症患者的异位子宫内膜中,ILC3与腺上皮细胞和内皮细胞的距离更远,这表明这些细胞可能较少接触到ILC3的产物,从而可能对子宫内膜再生产生负面影响。我们的研究结果突显了 ILC3 在子宫粘膜中的动态性质,并表明它们的主要作用是修复和再生。加深对子宫 ILC3 的了解将为未来有关子宫内膜健康和疾病的研究提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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