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Trophoblast-Derived CXCL16 Decreased Granzyme B Production of Decidual γδ T Cells and Promoted Bcl-xL Expression of Trophoblasts

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Abstract

Background

Decidual γδ T cells are known to regulate the function of trophoblasts at the maternal—fetal interface; however, little is known about the molecular mechanisms of cross talk between trophoblast cells and decidual γδ T cells.

Methods

Expression of chemokine C-X-C motif ligand 6 (CXCL16) and its receptor CXCR6 was evaluated in first-trimester human villus and decidual tissues by immunohistochemistry. γδ T cells were isolated from first-trimester human deciduae and cocultured with JEG3 trophoblast cells. Cell proliferation and apoptosis-related molecules, together with cytotoxicity factor and cytokine production, were measured by flow cytometry analysis.

Results

Expression of CXCL16 and CXCR6 was reduced at the maternal—fetal interface in patients who experienced unexplained recurrent spontaneous abortion as compared to healthy pregnancy women. With the administration of pregnancy-related hormones or coculture with JEG3 cells, CXCR6 expression was upregulated on decidual γδ T cells. CXCL16 derived from JEG3 cells caused a decrease in granzyme B production of decidual γδ T cells. In addition, decidual γδ T cells educated by JEG3-derived CXCL16 upregulated the expression of Bcl-xL in JEG3 cells.

Conclusion

This study suggested that the CXCL16/CXCR6 axis may contribute to maintaining normal pregnancy by reducing the secretion of cytotoxic factor granzyme B of decidual γδ T cells and promoting the expression of antiapoptotic marker Bcl-xL of trophoblasts.

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Author information

Authors and Affiliations

  1. Obstetrics and Gynecology Hospital, Fudan University, 358 Dalin Road, Shanghai, 200011, People’s Republic of China

    Deng-Xuan Fan MD, Wen-Jie Zhou MD, Ming-Qing Li PhD & Cong-Jian Xu MD, PhD

  2. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 2699 West Gaoke Road, Shanghai, 201204, People’s Republic of China

    Li-Ping Jin MD, PhD & Xiang-Hong Xu PhD

  3. Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, People’s Republic of China

    Cong-Jian Xu MD, PhD

  4. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Fudan University, Shanghai, People’s Republic of China

    Cong-Jian Xu MD, PhD

Authors
  1. Deng-Xuan Fan MD
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  2. Wen-Jie Zhou MD
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  3. Li-Ping Jin MD, PhD
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  4. Ming-Qing Li PhD
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  5. Xiang-Hong Xu PhD
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  6. Cong-Jian Xu MD, PhD
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Corresponding authors

Correspondence to Xiang-Hong Xu PhD or Cong-Jian Xu MD, PhD.

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Authors’ Note

Deng-Xuan Fan and Wen-Jie Zhou contributed equally to this work.

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Fan, DX., Zhou, WJ., Jin, LP. et al. Trophoblast-Derived CXCL16 Decreased Granzyme B Production of Decidual γδ T Cells and Promoted Bcl-xL Expression of Trophoblasts. Reprod. Sci. 26, 532–542 (2019). https://doi.org/10.1177/1933719118777638

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  • DOI: https://doi.org/10.1177/1933719118777638

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