Indoleamine 2,3-dioxygenase suppresses the cytotoxicity of NK cells in response to ectopic endometrial stromal cells in endometriosis

Xuan-Tong Liu, Liu XT, Huiting Sun, Sun HT, Hui-Ting Sun, Zhong-Fang Zhang, Zhang ZF, Zhongfang Zhang, Ru-Xia Shi, Shi RX, Ruxia Shi, Libing Liu, Liu LB, Li-Bing Liu, Jia-Jun Yu, Yu JJ, Jiajun Yu, Zhou WJ, Wen-Jie Zhou, Wen‐Jie Zhou, Chunjie Gu, Gu CJ, Chun-Jie Gu, Shao-Liang Yang, Yang SL, Shao‐Liang Yang, Liu YK, Yu-Kai Liu, Yukai Liu, Hui‐Li Yang, Yang HL, Hui-Li Yang, Feng-Xuan Xu, Xu FX, Ming-Qing Li, Ming‐Qing Li
Reproduction (Cambridge, England) · 2018 · vol. 156(5) , pp. 397–404 · doi:10.1530/rep-18-0112 · PMID:30087159 · W2887800031
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Endometrial stromal cells induce indoleamine 2,3-dioxygenase expression in NK cells, suppressing their cytotoxicity towards ectopic endometrial stromal cells in endometriosis.

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Abstract

It has been reported that the impaired cytotoxicity of natural killer (NK) cells and abnormal cytokines that are changed by the interaction between ectopic endometrial cells and immune cells is indispensable for the initiation and development of endometriosis (EMS). However, the mechanism of NK cells dysfunction in EMS remains largely unclear. Here, we found that NK cells in peritoneal fluid from women with EMS highly expressed indoleamine 2,3-dioxygenase (IDO). Furthermore, IDO+NK cells possessed lower NKp46 and NKG2D but higher IL-10 than that of IDO-NK. Co-culture with endometrial stromal cells (nESCs) from healthy control or ectopic ESCs (eESCs) from women with EMS led to a significant increase in the IDO level in NK cells from peripheral blood, particularly eESCs, and an anti-TGF-β neutralizing antibody suppressed these effects in vitro. NK cells co-cultured with ESC more preferentially inhibited the viability of nESCs than eESCs did, and pretreating with 1-methyl-tryptophan (1-MT), an IDO inhibitor, reversed the inhibitory effect of NK cells on eESC viability. These data suggest that ESCs induce IDO+NK cells differentiation partly by TGF-β, and that IDO further restricts the cytotoxicity of NK cells in response to eESCs, which provides a potential therapeutic strategy for EMS patients, particularly those with a high number of impaired cytotoxic IDO+NK cells.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Indoleamine-Pyrrole 2,3,-Dioxygenase Killer Cells, Natural Adult Ascitic Fluid Ascitic Fluid Case-Control Studies Cells, Cultured Endometriosis Endometrium Endometrium Female Humans Indoleamine-Pyrrole 2,3,-Dioxygenase Killer Cells, Natural Middle Aged Natural Cytotoxicity Triggering Receptor 1 Natural Cytotoxicity Triggering Receptor 1 NK Cell Lectin-Like Receptor Subfamily K

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