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The imbalance of Th17/Treg axis involved in the pathogenesis of preeclampsia
Author(s) -
EghbalFard Shadi,
Yousefi Mehdi,
Heydarlou Hanieh,
Ahmadi Majid,
Taghavi Simin,
Movasaghpour Aliakbar,
JadidiNiaragh Farhad,
Yousefi Bahman,
Dolati Sanam,
HojjatFarsangi Mohammad,
Rikhtegar Reza,
Nouri Mohammad,
AghebatiMaleki Leili
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27315
Subject(s) - immune system , rar related orphan receptor gamma , pathogenesis , peripheral blood mononuclear cell , immunology , flow cytometry , retinoic acid , preeclampsia , interleukin 17 , reverse transcription polymerase chain reaction , interleukin , receptor , microrna , pathophysiology , orphan receptor , endocrinology , biology , transcription factor , medicine , messenger rna , cytokine , gene , foxp3 , pregnancy , in vitro , genetics
Abstract Problem Inappropriate activation of the immune system, particularly the imbalance of T‐helper type 17 (Th17)/regulatory T (Treg) cells is thought to play considerable roles in preeclampsia (PE). To investigate the probable effects of the adaptive immune system in the pathophysiology of PE, we analyzed the dynamic changes of Th17/Treg cells, cytokines profile, and transcription pattern of Th17/Treg‐related genes and microRNAs (miRNAs) in 50 women suffering from PE in comparison with 50 healthy pregnant women. Methods Expressions of cytokines, specific transcription factors, and related miRNAs were measured by real‐time polymerase chain reaction (PCR). Enzyme‐linked immunosorbent assay (ELISA) was used to test the interleukin (IL)‐17, IL‐23, IL‐6, and IL‐10 and transforming growth factor β in serum and supernatant of peripheral blood mononuclear cells (PBMCs). The frequency of Th17 and Treg cells were determined by flow cytometry. Results PE patients exhibited a decreased number of Treg cells ( p = 0.006), while Th17 cells were increased ( p = 0.004). Forkhead box P3 and IL‐10 mRNA expressions were reduced ( p = 0.0001 and 0.0028, respectively), while expressions of retinoic acid receptor‐related orphan nuclear receptor γt, IL‐17, IL‐23, and IL‐6 were enhanced ( p < 0.0001, 0.0018, 0.0014, and 0.027, respectively). ELISA results also showed increased levels of IL‐6, IL‐17, and IL‐23 ( p = 0.022, 0.0005, 0.0081, respectively), and decreased levels of IL‐10 in the supernatant of PBMCs of PE patients compared with control group ( p = 0.0011). There was significant upregulation of miR‐106b and miR‐326 ( p = 0.0048 and 0.028, respectively) in PE patients in comparison with the control group. Conclusions These findings suggest that imbalance of Th17/Treg cells, regulated possibly via microRNAs, may be involved in the pathogenesis of PE, emphasizing on the importance of these cells in feto‐maternal immune cross‐talk.