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Preeclampsia-Derived Exosomes Imbalance the Activity of Th17 and Treg in PBMCs from Healthy Pregnant Women

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Abstract

The disturbance of maternofetal immune tolerance is identified as one of the important issues in the pathology of preeclampsia (PE). PE exosomes are believed to possess significant roles in immune abnormalities. In this study, to assess the possible effects of PE exosomes in the pathophysiology of preeclampsia patients, exosomes were isolated from the serum of PE patients and incubated with peripheral blood mononuclear cells (PBMCs) of healthy pregnant women. Also, exosomes from healthy pregnant women were utilized as the control. Th17/Treg ratio in PE and healthy pregnant women and the effects of PE exosomes on expression level of Th17 and Treg transcription factors, as well as their related cytokines in PBMCs of healthy pregnant women, were evaluated. A significant decrease in Treg cell number and increase in Th17 cells and Th17/Treg ratio were observed in PE patients. Following PE-exosome intervention, a significant increase in mRNA expression level of RORγt, IL-17, IL-23, IL-1β, and IL-6, and significant decrease in IL-10 and TGFβ were evident. On the other hand, no significant difference in FoxP3 level was detected. Additionally, increased IL-6, IL-17, IL-23, and IL-1β levels and decreased IL-10 level in the supernatant of cultured PBMCs from healthy pregnant women following PE-exosome intervention were exhibited. However, TGF-β level did not change significantly. Based on our findings, PE exosomes are able to alter the activity of Th17 and Treg cells as well as their related gene expression and cytokine profiles. These findings support the probable role of PE exosomes in PE pathogenesis.

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Data Availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Code Availability

Not applicable.

Abbreviations

PE:

Preeclampsia

PBMCs:

Peripheral blood mononuclear cells

Th:

T helper

NKT:

Natural killer T cell

RORγt:

Retinoic acid receptor–related orphan nuclear receptor γt

FoxP3:

Fork-head box P3

IL:

Interleukin

TGF-β:

Transforming growth factor

ELISA:

Enzyme-linked immunosorbent assay

HRP:

Horseradish peroxidase

AP:

Alkaline phosphatase

PMA:

Phorbol myristate acetate

cDNA:

Complementary DNA

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Funding

This study was supported by National Institute for Medical Research Development (NIMAD) with Grant number 982743.

Author information

Author notes

  1. Ramin Pourakbari and Forough Parhizkar contributed equally to this work.

Authors and Affiliations

  1. Student’s Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Ramin Pourakbari

  2. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Ramin Pourakbari & Mehdi Yousefi

  3. Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran

    Forough Parhizkar, Mohammad Sadegh Soltani‐Zangbar, Farhad Jadidi-Niaragh & Mehdi Yousefi

  4. Hematology Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Parisa Samadi

  5. Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Gonabad University of Medical Sciences, Gonabad, Iran

    Majid Zamani

  6. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Leili Aghebati-Maleki

  7. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Roza Motavalli

  8. Anesthesiology Research Team, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Ata Mahmoodpoor

  9. Molecular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Bahman Yousefi

  10. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Hossein Samadi Kafil

  11. Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm, Sweden

    Mohammad Hojjat-Farsangi

  12. Gynecology Department, ACECR ART Centre, Eastern Azerbaijan Branch of ACECR, Tabriz, Iran

    Shahla Danaii

Authors
  1. Ramin Pourakbari
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Contributions

Mehdi Yousefi and Leili Aghebati-Maleki are principal investigators who supervised the study. Ramin Pourakbari and Forough Parhizkar participated in drafting the manuscript. Mohammad Sadegh Soltani‐Zangbar, Parisa Samadi, Majid Zamani, Roza Motavalli, Ata Mahmoodpoor, Farhad Jadidi-Niaragh, Bahman Yousefi, and Hossein Samadi Kafil were involved in data collection and conducted molecular experiments and RT-qPCR analysis; Shahla Danaii participated in patient selection and revised the draft critically. Mohammad Hojjat-Farsangi helped in the study design. Each author approved the final manuscript for submission.

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Correspondence to Leili Aghebati-Maleki or Mehdi Yousefi.

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Pourakbari, R., Parhizkar, F., Soltani‐Zangbar, M.S. et al. Preeclampsia-Derived Exosomes Imbalance the Activity of Th17 and Treg in PBMCs from Healthy Pregnant Women. Reprod. Sci. 30, 1186–1197 (2023). https://doi.org/10.1007/s43032-022-01059-x

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