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IL-17A and Th17 Cells Contribute to Endometrial Cell Survival by Inhibiting Apoptosis and NK Cell Mediated Cytotoxicity of Endometrial Cells via ERK1/2 Pathway

  • Young-Ju Kang (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Hee Jun Cho (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Yunhee Lee (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Arum Park (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Mi Jeong Kim (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • In Cheul Jeung (Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea) ;
  • Yong-Wook Jung (Department of Obstetrics and Gynecology, CHA Gangnam Medical Center) ;
  • Haiyoung Jung (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Inpyo Choi (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Hee Gu Lee (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Suk Ran Yoon (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2021.12.29
  • Accepted : 2022.12.12
  • Published : 2023.04.30
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Abstract

Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients. To determine the roles of IL-17A and Th17 cells in the development of endometriosis, the effect of IL-17A, major cytokine of Th17, on endometrial cells isolated from endometriotic tissues was examined. Recombinant IL-17A promoted survival of endometrial cells accompanied by increased expression of anti-apoptotic genes, including Bcl-2 and MCL1, and the activation of ERK1/2 signaling. In addition, treatment of IL-17A to endometrial cells inhibited NK cell mediated cytotoxicity and induced HLA-G expression on endometrial cells. IL-17A also promoted migration of endometrial cells. Our data suggest that Th17 cells and IL-17A play critical roles in the development of endometriosis by promoting endometrial cell survival and conferring a resistance to NK cell cytotoxicity through the activation of ERK1/2 signaling. Targeting IL-17A has potential as a new strategy for the treatment of endometriosis.

Keywords

Acknowledgement

We would like to thank Jung-Hyeon Choi (Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology [KRIBB]) for technical assistance with immunohistochemistry. This work was supported by grants from the grant of National Research Foundation of Korea (NRF) (2019R1A2C1007906) and KRIBB Research Initiative Program from the Korea government.

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