IL15 promotes growth and invasion of endometrial stromal cells and inhibits killing activity of NK cells in endometriosis

Jia-Jun Yu, Jiajun Yu, Hui-Ting Sun, Huiting Sun, Zhong-Fang Zhang, Zhongfang Zhang, Ruxia Shi, Ru-Xia Shi, Libing Liu, Li-Bing Liu, Wen-Qing Shang, Chun-Yan Wei, Chunyan Weı, Kai-Kai Chang, Kai‐Kai Chang, Jun Shao, Ming-Yan Wang, Mingyan Wang, Ming‐Qing Li, Ming-Qing Li
Reproduction (Cambridge, England) · 2016 · vol. 152(2) , pp. 151–160 · doi:10.1530/rep-16-0089 · PMID:27190213 · W2405623683
article OA: bronze CC0 ⤵ 67 in-corpus citations
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Interleukin-15 derived from endometrial stromal cells promotes their growth and invasion while suppressing natural killer cell cytotoxicity, facilitating endometriosis progression.

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Abstract

Endometriosis (EMS) is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissues. It has been reported that human endometrial stromal cells (ESCs) express interleukin (IL)15. The aim of our study was to elucidate whether or not IL15 regulates the cross talk between ESCs and natural killer (NK) cells in the endometriotic milieu and, if so, how this regulation occurs. The ESC behaviors in vitro were verified by Cell Counting Kit-8 (CCK-8), Annexin/PI, and Matrigel invasion assays, respectively. To imitate the local immune microenvironment, the co-culture system between ESCs and NK cells was constructed. The effect of IL15 on NK cells in the co-culture unit was investigated by flow cytometry (FCM). In this study, we found that ectopic endometrium from patients with EMS highly expressed IL15. Rapamycin, an autophagy inducer, decreased the level of IL15 receptors (i.e. IL15Rα and IL2Rβ). IL15 inhibits apoptosis and promotes the invasiveness, viability, and proliferation of ESCs. Meanwhile, a co-culture with ESCs led to a decrease in CD16 on NK cells. In the co-culture system, IL15 treatment downregulated the levels of Granzyme B and IFN-γ in CD16(+)NK cells, NKG2D in CD56(dim)CD16(-)NK cells, and NKP44 in CD56(bright)CD16(-)NK cells. On the one hand, these results indicated that IL15 derived from ESCs directly stimulates the growth and invasion of ESCs. On the other hand, IL15 may help the immune escape of ESCs by suppressing the cytotoxic activity of NK cells in the ectopic milieu, thereby facilitating the progression of EMS.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Interleukin-15 Killer Cells, Natural Stromal Cells Adult Case-Control Studies Cell Proliferation Cells, Cultured Coculture Techniques Down-Regulation Endometriosis Endometriosis Endometrium Endometrium Female Humans Interleukin-15 Killer Cells, Natural Killer Cells, Natural

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