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PD-1 mediates decidual γδ T cells cytotoxicity during recurrent pregnancy loss.

  • Guo, Rong1, 2
  • Jiang, Silin3
  • Zhang, Jianliang1
  • Yang, Quanli4, 5
  • Gao, Liang6
  • Xia, Wei1
  • Tong, Lingxia1
  • Feng, Peiran4
  • Xu, Yan4
  • Zhang, Tao7
  • Cheng, Hao8, 9
  • Liu, CuiPing10
  • Zhang, Xueguang10
  • Yin, Zhinan3, 4, 5
  • Zhang, Hong1, 10
  • 1 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China. , (China)
  • 2 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China. , (China)
  • 3 National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, Guangxi, China. , (China)
  • 4 The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, Guangdong, China. , (China)
  • 5 Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, Guangdong, China. , (China)
  • 6 The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China. , (China)
  • 7 Department of Obstetrics and Gynecology, Weifang Traditional Chinese Hospital, Weifang, Shandong, China. , (China)
  • 8 Center for Cancer Immunology Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China. , (China)
  • 9 Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China. , (China)
  • 10 Jiangsu Institute of Clinical Immunology & Jiangsu Key Laboratory of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China. , (China)
Published Article
American journal of reproductive immunology (New York, N.Y. : 1989)
Publication Date
May 14, 2022
DOI: 10.1111/aji.13562
PMID: 35567369


Recurrent pregnancy loss (RPL) is one of the big challenges of normal pregnancy. Immune dysregulation has been proposed for the key underline mechanisms of RPL. However, the essential roles of T cells, especially γδ T cells, have not been defined. Decidua were obtained from normal pregnancy women or recurrent pregnancy loss patients and the surface molecules of γδ T cells in decidua were evaluated via flow cytometric analysis. The expression of PD-1 in clinical samples was analyzed by immunohistochemistry assay. The intracellular cytokines of decidual PD-1+ and PD-1- γδ T cells were evaluated by flow cytometric analysis. The cytotoxicity of PD-1- γδ T cells were confirmed via an in vitro co-culture experiment. The specific inhibitors for Erk, p38 and JNK against the MAPK pathway were added to the co-culture media to evaluate the functions of the Erk, p38 and JNK. We demonstrated that PD-1 was significantly decreased on decidual tissue γδ T cells of patients with RPL, resulting in the enhanced cytotoxicity of γδ T cells against trophoblasts. We further elucidated an Erk-dependent TNF-α production mediates the γδ T cell cytotoxicity against the trophoblast cells. Finally, the reduced expression of PD-L1 in the villi tissues of patients with RPL might be the cause of the reduction of PD-1 on the tissue γδ T cells. Our study uncovers an important role of PD-1 expression on decidual γδ T cells in maintaining the normal pregnancy, and may provide a new strategy for immune therapy against RPL. © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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