Indoleamine 2,3-dioxygenase suppresses the cytotoxicity of 1 NK cells in response to ectopic endometrial stromal cells in endometriosis

Liu, Xuan-Tong; Sun, Huiting; Shi, Ran; Liu, Libing; Yu, Jiajun; Zhou, Wen‐Jie; Gu, Chunjie; Yang, Shao-Liang; Liu, Yukai; Yang, Hui‐Li; Xu, Feng-Xuan; Li, Ming‐Qing

doi:10.1530/rep-18-0112

Cited by 14 publications

(14 citation statements)

References 39 publications

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“…Currently, the cause of reduced immunosurveillance of endometriotic lesions in the pelvic cavity of women with endometriosis is unknown. One of the components of this reduced immunosurveillance is the inhibition of NK cells (Oosterlynck et al, 1991;Oosterlynck et al, 1992;Liu et al, 2018;Xu, 2019). Therefore, in the present study, we investigated if ESC cyst may also be involved in NK cell-mediated inhibition, because we previously found that they may possess immunosuppressive properties (Abomaray et al, 2017).…”

Section: Discussionmentioning

confidence: 96%

“…However, it seems that the effects on the NK cells are mostly mediated through macrophages and not ESC cyst , since NK cell cytotoxicity was not reduced following coculture with only ESC cyst (Yang et al, 2017). In another study, NK cells were cultured with ESC endohv or ectopic ESC; it was found that the NK cells significantly enhanced their expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), especially following culture with ectopic ESC, and the effect was partly due to ESC-derived TGFβ1 (Liu et al, 2018). Moreover, when the NK cells were in turn cultured with ectopic ESC, their cytotoxicity was significantly inhibited, and this was attributed to their expression of IDO (Liu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have found that NK cells are inhibited in the pelvic cavity of women with endometriosis (Oosterlynck et al, 1991;Oosterlynck et al, 1992;Liu et al, 2018) and that the peritoneal fluid in women with endometriosis may contain certain factors that are inhibiting the function of NK cells (Oosterlynck et al, 1993;Kang et al, 2014). In addition, some studies have examined interactions between NK cells and ectopic MSC (Yu et al, 2016;Yang et al, 2017;Liu et al, 2018), suggesting that stromal cells may be involved in the inhibition of NK cells in the pelvic cavity in women with endometriosis. However, a comparison of the effects of stromal cells from endometriotic ovarian cysts (ESC cyst ) and the endometrium (ESC endo ) of women with endometriosis on NK cells in vitro has not been carried out previously.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Mesenchymal Stromal Cells Derived From Endometriotic Lesions on Natural Killer Cell Function

Abomaray

Wagner

Chrobok

et al. 2021

Front. Cell Dev. Biol.

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Endometriosis is an inflammatory disease that presents with ectopic endometriotic lesions. Reduced immunosurveillance of these lesions has been proposed to be playing a role in the pathology of endometriosis. Mesenchymal stromal cells (MSC) are found in ectopic lesions and may decrease immunosurveillance. In the present study, we examined if MSC contribute to reduced immunosurveillance through their immunosuppressive effects on natural killer (NK) cells. Stromal cells from endometriotic ovarian cysts (ESCcyst) and eutopic endometrium (ESCendo) of women with endometriosis and their conditioned medium were used in co-cultures with allogeneic peripheral blood NK cells. Following culture, NK cells were examined phenotypically for their expression of activating, inhibitory, maturation, and adhesion receptors and co-receptors, as well as the degranulation (CD107a) marker and the immunostimulatory (interferon-γ) and immunosuppressive (transforming growth factor beta 1 and interleukin-10) cytokines. Moreover, NK cell cytotoxicity was examined using chromium 51 release killing assays. There were no differences between ESCcyst and ESCendo regarding their effects on NK cell cytotoxicity in both conditioned medium and direct co-culture experiments. Additionally, there were no differences between ESCcyst and ESCendo regarding their impact on NK cells’ phenotype and degranulation in both conditioned medium and direct co-culture experiments. Although there were no differences found for DNAX accessory molecule-1 (DNAM-1) and NKp44, we found that the expression of the NK cell ligand CD155 that binds DNAM-1 and proliferating cell nuclear antigen (PCNA) that binds NKp44 was significantly less on ESCcyst than on ESCendo. These findings were not supported by the results that the expression of the known and unknown ligands on ESCcyst for DNAM-1 and NKp44 using chimeric proteins was not significantly different compared to ESCendo. In conclusion, the results suggest that ectopic MSC may not contribute to reduced immunosurveillance in endometriosis through their inhibitory effects on NK cells. This suggests that NK cell inhibition in the pelvic cavity of women with endometriosis develops due to other factors.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Effect of Mesenchymal Stromal Cells Derived From Endometriotic Lesions on Natural Killer Cell Function

Abomaray

Wagner

Chrobok

et al. 2021

Front. Cell Dev. Biol.

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“…This is an important observation indicating that the cultured cells retain malignant phenotype with high IDO1 [ 24 , 44 ] and HER2 expression observed in vivo [ 59 ]. Together, it makes this model suitable for identification and testing novel immunotherapeutics for HER2- and IDO1-associated pathology shown to be important in endometrial cancer [ 45 ] or endometriosis [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Activation of the kynurenine pathway (KP), responsible for the generation of several toxic metabolites called kynurenines, modulates local immune tolerance [ 20 , 21 ]. IDO1 activity is of great interest for scientists studying biology and pathology of endometrium [ 22 ]. Recently, KP has been also recognized as a novel factor in endometrial cancer tissue [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Factors in Primary Endometrial Cell Cultures Isolated from Cancer and Noncancerous Human Tissue–Focus on RAGE and IDO1

Tkaczuk-Włach

Kędzierski

Jonik

et al. 2021

Cells

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Background: Immune modulatory factors like indoleamine 2,3-dioxygenase 1 (IDO1) generating kynurenine (Kyn) and receptor for advanced glycation end-products (RAGE) contribute to endometrial and cancer microenvironment. Using adequate experimental models is needed to learn about the significance of these molecular factors in endometrial biology. In this paper we study IDO1 activity and RAGE expression in the in vitro cultured primary human endometrial cells derived from cancerous and noncancerous tissue. Methods: The generated primary cell cultures from cancer and noncancerous endometrial tissues were characterized using immunofluorescence and Western Blot for expression of endometrial and cancer markers. IDO1 activity was studied by Kyn quantification with High Performance Liquid Chromatography with Diode Array Detector. Results: The primary cultures of endometrial cells were obtained with 80% success rate and no major genetic aberrations. The cells retained in vitro expression of markers (mucin MUC1 and HER2) or immunomodulatory factors (RAGE and IDO1). Increased Kyn secretion was associated with cancer endometrial cell culture in contrast to the control one. Conclusions: Primary endometrial cells express immune modulatory factors RAGE and IDO1 in vitro associated with cancer phenotype of endometrium.

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Anti-inflammatory cytokines in endometriosis

Zhou¹,

Yang²,

Shao³

et al. 2019

Cell. Mol. Life Sci.

122

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Indoleamine 2,3-dioxygenase suppresses the cytotoxicity of 1 NK cells in response to ectopic endometrial stromal cells in endometriosis

Cited by 14 publications

References 39 publications

The Effect of Mesenchymal Stromal Cells Derived From Endometriotic Lesions on Natural Killer Cell Function

The Effect of Mesenchymal Stromal Cells Derived From Endometriotic Lesions on Natural Killer Cell Function

Immunomodulatory Factors in Primary Endometrial Cell Cultures Isolated from Cancer and Noncancerous Human Tissue–Focus on RAGE and IDO1

Anti-inflammatory cytokines in endometriosis

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