The crosstalk between endometrial stromal cells and macrophages impairs cytotoxicity of NK cells in endometriosis by secreting IL-10 and TGF-β

Hui-Li Yang, Hui‐Li Yang, Wen-Jie Zhou, Wen‐Jie Zhou, Kai‐Kai Chang, Kai-Kai Chang, Jie Mei, Li-Qing Huang, Liqing Huang, Ming-Yan Wang, Mingyan Wang, Yi Meng, Si-Yao Ha, Siyao Ha, Da-Jin Li, Da‐Jin Li, Ming‐Qing Li, Ming-Qing Li
Reproduction (Cambridge, England) · 2017 · vol. 154(6) , pp. 815–825 · doi:10.1530/rep-17-0342 · PMID:28971893 · W2763551307
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Endometrial stromal cells and macrophages in endometriosis impair NK cell cytotoxicity by secreting IL-10 and TGF-β, contributing to immune escape.

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Abstract

Abstract The dysfunction of NK cells in women with endometriosis (EMS) contributes to the immune escape of menstrual endometrial fragments refluxed into the peritoneal cavity. The reciprocal communications between endometrial stromal cells (ESCs) and lymphocytes facilitate the development of EMS. However, the mechanism of these communications on cytotoxicity of natural killer (NK) cells in endometriotic milieus is still largely unknown. To imitate the local immune microenvironment, the co-culture systems of ESCs from patients with EMS and monocyte-derived macrophages or of ESCs, macrophages and NK cells were constructed. The cytokine levels in the co-culture unit were evaluated by ELISA. The expression of functional molecules in NK cells was detected by flow cytometry (FCM). The NK cell behaviors in vitro were analyzed by cell counting kit-8 and cytotoxic activation assays. After incubation with ESCs and macrophages, the expression of CD16, NKG2D, perforin and IFN-γ, viability and cytotoxicity of NK cells were significantly downregulated. The secretion of interleukin (IL)-1β, IL-10 and transforming growth factor (TGF)-β in the co-culture system of ESCs and macrophages was increased. Exposure with anti-IL-10 receptor β neutralizing antibody (αhIL-10Rβ) or αTGF-β could partly reverse these effects of ESCs and macrophages on NK cells in vitro. These results suggest that the interaction between macrophages and ESCs downregulates cytotoxicity of NK cells possibly by stimulating the secretion of IL-10 and TGF-β, and may further trigger the immune escape of ectopic fragments and promote the occurrence and the development of EMS.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometrium Interleukin-10 Killer Cells, Natural Macrophages Paracrine Communication Stromal Cells Transforming Growth Factor beta Adult Cells, Cultured Cellular Microenvironment Coculture Techniques Cytotoxicity, Immunologic Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Female

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