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Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium
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Brighton, Paul (Paul J.), Maruyama, Yojiro, Fishwick, Katherine, Vrljicak, Pavle, Tewary, Shreeya, Fujihara, Risa, Muter, Joanne, Lucas, Emma S., Yamada, Taihei, Woods, Laura, Lucciola, Raffaella, Lee, Yie Hou, Takeda, Satoru, Ott, Sascha, Hemberger, Myriam, Quenby, Siobhan and Brosens, Jan J. (2017) Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. eLife, 6 . e31274. doi:10.7554/eLife.31274 ISSN 2050-084X.
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Official URL: https://doi.org/10.7554/eLife.31274
Abstract
In cycling human endometrium, menstruation is followed by rapid estrogen-dependent growth. Upon ovulation, progesterone and rising cellular cAMP levels activate the transcription factor Forkhead box O1 (FOXO1) in endometrial stromal cells (EnSCs), leading to cell cycle exit and differentiation into decidual cells that control embryo implantation. Here we show that FOXO1 also causes acute senescence of a subpopulation of decidualizing EnSCs in an IL-8 dependent manner. Selective depletion or enrichment of this subpopulation revealed that decidual senescence drives the transient inflammatory response associated with endometrial receptivity. Further, senescent cells prevent differentiation of endometrial mesenchymal stem cells in decidualizing cultures. As the cycle progresses, IL-15 activated uterine natural killer (uNK) cells selectively target and clear senescent decidual cells through granule exocytosis. Our findings reveal that acute decidual senescence governs endometrial rejuvenation and remodeling at embryo implantation, and suggest a critical role for uNK cells in maintaining homeostasis in cycling endometrium.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QP Physiology | |||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | |||||||||
| Library of Congress Subject Headings (LCSH): | Endometrium, Endometrium -- Diseases, Fertility, Human, Ovum implantation, Fertilization in vitro, Human, Killer cells | |||||||||
| Journal or Publication Title: | eLife | |||||||||
| Publisher: | eLife Sciences Publications Ltd. | |||||||||
| ISSN: | 2050-084X | |||||||||
| Book Title: | Clearance of senescent decidual cells by uterine natural killer cells drives endometrial remodeling during the window of implantation | |||||||||
| Official Date: | 11 December 2017 | |||||||||
| Dates: |
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| Volume: | 6 | |||||||||
| Article Number: | e31274 | |||||||||
| DOI: | 10.7554/eLife.31274 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Date of first compliant deposit: | 6 December 2017 | |||||||||
| Date of first compliant Open Access: | 6 March 2018 | |||||||||
| RIOXX Funder/Project Grant: |
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