Altered Expression of STAT3, RORγt, and IL-17A Proteins and Th17 Cell in Intrahepatic Cholestasis of Pregnancy

² Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, 610000 Chengdu, Sichuan, China

³ Department of Gynaecology and Obstetrics, West China Second University Hospital, Sichuan University, 610000 Chengdu, Sichuan, China

^*Correspondence: yayi.hu@163.com (Ya-Yi Hu)
Academic Editor: Paolo Ivo Cavoretto

Clin. Exp. Obstet. Gynecol. 2022, 49(7), 163; https://doi.org/10.31083/j.ceog4907163

Submitted: 23 April 2022 | Revised: 31 May 2022 | Accepted: 2 June 2022 | Published: 13 July 2022

This is an open access article under the CC BY 4.0 license.

Abstract

Background: Intrahepatic cholestasis of pregnancy (ICP) is a disorder specifically associated with pregnancy. Recent evidence suggests that the T helper 17 (Th17) cell population is related to a maternal and foetal immune imbalance associated with ICP. However, there has been insufficient attention paid to the potential roles of signal transducer and activator of transcription 3 (STAT3) and RAR-related orphan receptor gamma (ROR $\gamma$ t) in modulations of Th17 cell in ICP. Accordingly, the purpose of our study was to investigate the alterations of Th17 cell in placenta and peripheral blood of patients with ICP and correlations between Th17 cell and STAT3, ROR $\gamma$ t, interleukin (IL)-17A in ICP. Methods: Nine pregnant women with ICP and nine women with normal pregnancy served as the ICP and control groups, respectively. STAT3, ROR $\gamma{}$ t, and IL-17A expression were examined by immunohistochemistry and western blotting in placental tissue. Flow cytometry was used to quantify Th17 cell in blood of peripheral circulation. We compared data between groups using Chi-square tests or paired t tests. Pearson or Spearman coefficients were used to measure correlations. Results: STAT3, ROR $\gamma{}$ t, and IL-17A were mainly expressed in the trophoblasts of the two groups of patients. Comparatively to the control group, placental levels of STAT3, ROR $\gamma{}$ t, and IL-17A proteins were significantly elevated in ICP group, as was maternal levels of Th17 cell in peripheral blood. Moreover, placental IL-17A protein level showed significantly positive relationships with placental STAT3 (r = 0.97, p = 2e-05) and ROR $\gamma$ t (r = 0.91, p = 0.01) protein in control group, however, not in ICP group (STAT3, r = 0.5, p = 0.17; ROR $\gamma$ t, r = 0.62, p = 0.07). Conclusions: Women with ICP showed an increase in Th17 cells in comparison to women with normal pregnancies. STAT3 and ROR $\gamma{}$ t may increase Th17 cell proliferation and differentiation, appears to be altered in ICP. ICP may be adversely affected by excessive accumulation of Th17 cell.

Keywords

correlation

intrahepatic cholestasis of pregnancy

signal transducer and activator of transcription 3

T helper cell-17

Funding

2022YFS0043/Applied Research in China Sichuan Province

2020CDZG-23/Applied Research in China Sichuan Province

KL107/Clinical research fund of West China Second University Hospital

Figures

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Fig. 1.

STAT3, ROR $\gamma$ t, and IL 17A protein distribution in the placenta of the two groups (nine samples per group). (A,B) Hematoxylin and eosin staining of the blank control group. (C,D) ROR $\gamma$ t protein in the cytoplasm of placental trophoblasts in control and ICP groups. (E,F) STAT3 protein distributed in both the nucleus and cytoplasm of trophoblasts in the two groups. (G,H) IL-17A protein located in the cytoplasm of placental trophoblasts in both groups. All images were acquired following immunohistochemical analysis at 400 $\times$ magnification.

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