Role of Transforming Growth Factor-β1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy

Dongyong Yang, Fangfang Dai, Mengqin Yuan, Yajing Zheng, Shiyi Liu, Zhimin Deng, Wei Tan, Liping Chen, Qianjie Zhang, Xiaomiao Zhao, Yanxiang Cheng, Dongyong Yang, Fangfang Dai, Mengqin Yuan, Yajing Zheng, Shiyi Liu, Zhimin Deng, Wei Tan, Liping Chen, Qianjie Zhang, Xiaomiao Zhao, Yanxiang Cheng

Abstract

Transforming growth factor-β (TGF-β) is composed of three isoforms, TGF-β1, TGF-β2, and TGF-β3. TGF-β1 is a cytokine with multiple biological functions that has been studied extensively. It plays an important role in regulating the differentiation of immune cells and maintaining immune cell functions and immune homeostasis. Pregnancy is a carefully regulated process. Controlled invasion of trophoblasts, precise coordination of immune cells and cytokines, and crosstalk between trophoblasts and immune cells play vital roles in the establishment and maintenance of normal pregnancy. In this systematic review, we summarize the role of TGF-β1 in regulating fetal-maternal immune tolerance in healthy and pathological pregnancies. During healthy pregnancy, TGF-β1 induces the production of regulatory T cells (Tregs), maintains the immunosuppressive function of Tregs, mediates the balance of M1/M2 macrophages, and regulates the function of NK cells, thus participating in maintaining fetal-maternal immune tolerance. In addition, some studies have shown that TGF-β1 is dysregulated in patients with recurrent spontaneous abortion or preeclampsia. TGF-β1 may play a role in the occurrence and development of these diseases and may be a potential target for the treatment of these diseases.

Keywords: immune tolerance; preeclampsia; pregnancy; recurrent spontaneous abortion; transforming growth factor-β1.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Yang, Dai, Yuan, Zheng, Liu, Deng, Tan, Chen, Zhang, Zhao and Cheng.

Figures

Figure 1
Figure 1
Active TGF-β1 functions via SMAD-dependent and/or SMAD-independent pathways. SMAD-dependent pathway: After TGF-β1 binds to specific receptors on the cell surface, phosphorylated TβR-I recruits and phosphorylates SMAD2 and SMAD3. Phosphorylated SMAD2 and/or SMAD3 combine with SMAD4 to form a trimeric complex, which can regulate gene expression in the nucleus. SMAD-independent pathway: After TGF-β1 binds to receptors, phosphorylated TβR-I recruits and phosphorylates signaling molecules, such as PI3K-AKT, p38 MAPK, NF-κB, and ERK, and participates in the regulation of gene expression.

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