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Excessive Immune Activation and the Correlation with Decreased Expression of PD-1 at the Maternal–Fetal Interface in Preeclampsia

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Abstract

The etiology of preeclampsia (PE) is still unknown, and excessive immune activation is an important component of its pathogenesis. Programmed cell death protein 1 (PD-1) is one of immune checkpoints which may prevent overactivated immune attack and lead to a tolerant immune microenvironment. Little is known about the involvement of PD-1-mediated immunoregulation at the maternal–fetal interface in PE. To investigate the inflammatory pattern and the involvement of PD-1 in the decidua of women with PE, decidual tissues were obtained from PE and control pregnant women. Quantitative RT–PCR analysis of the mRNA levels of the inflammatory cytokines was performed. PD-1 expression was detected by immunohistochemistry, western blot analysis, and flow cytometry. To prove the role of PD-1, decidual immune cells were incubated with blocking antibodies, and the inflammatory cytokines were detected by ELISA. We observed that the mRNA levels of IL-1β, IL-6, TNF-α, and IFN-γ were higher in the decidua of the PE group than in the decidua of the control group. The mRNA levels of IL-4 and IL-10 were lower in PE. The expression level of PD-1 was significantly downregulated, and the proportion (%) of PD-1 + CD45 + cells was significantly lower in PE. There was a significant linear correlation between PD-1 expression and common proinflammatory cytokines in the decidua. Anti-PD-1 blocking antibody significantly increased the secretion of proinflammatory cytokines. Our data suggested that the inflammatory pattern and decreased PD-1 expression in the decidua might play an active role in the local immunoregulatory mechanisms of PE. The PD-1 pathway in the maternal–fetal interface possibly function to break the tolerant immune microenvironment in PE via inflammatory cytokines.

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Acknowledgements

The authors would like to thank all patients for their voluntary participation in this study and physicians at all study sites for their contribution.

Funding

This work was supported by the National Natural Science Foundation of China (81741038), the Jinan Science and Technology Program (201805025) and the Program from the Key Laboratory of Birth Regulation and Control Technology of National Health and Family Planning Commission of China (2021002).

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Author notes

  1. Shan Wang and Yining Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan, 250021, Shandong Province, China

    Shan Wang, Xiaoxiao Du & Jinlai Meng

  2. Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China

    Shan Wang, Yining Liu, Yue Liang, Yueyang Shi & Jinlai Meng

  3. Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China

    Lina Sun & Jinlai Meng

  4. Key Laboratory of Birth Regulation and Control Technology of National Health and Family Planning Commission of China, Maternal and Child Health Care Hospital of Shandong Province, Jinan, Shandong, China

    Jinlai Meng

Authors
  1. Shan Wang
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  2. Yining Liu
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Corresponding author

Correspondence to Jinlai Meng.

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Ethics Approval

This experiment was reviewed and approved by the Ethics Committee of Shandong Provincial Hospital.

Consent to Participate

All patients and their families voluntarily participated in this experiment and signed an informed consent form.

Consent for Publication

In the consent form, patients were informed that their data will be shared in summarized form grouped with other patients in published papers.

Conflict of Interest

The authors declare no competing interests.

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Wang, S., Liu, Y., Liang, Y. et al. Excessive Immune Activation and the Correlation with Decreased Expression of PD-1 at the Maternal–Fetal Interface in Preeclampsia. Reprod. Sci. 30, 192–202 (2023). https://doi.org/10.1007/s43032-022-01003-z

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  • DOI: https://doi.org/10.1007/s43032-022-01003-z

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