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The CXCL12/CXCR4 axis is involved in the maintenance of Th2 bias at the maternal/fetal interface in early human pregnancy

Cellular & Molecular Immunology volume 9, pages 423–430 (2012)Cite this article

Abstract

The regulatory mechanism of Th2 bias at the maternal/fetal interface remains unclear. In this study, we characterized cytokine production in decidual stromal cells (DSCs), decidual immune cells (DICs) and embryo-derived trophoblast cells, and investigated the regulation of CXCL12/CXCR4 interaction on Th2 bias at the maternal/fetal interface in early human pregnancy. We found differential production of Th1-type and Th2-type cytokines by trophoblasts, DSCs and DICs. The secretion of these cytokines varied in different cell cocultures, conduced to Th2 bias. Flow cytometry showed that coculture of trophoblasts with DSCs and DICs significantly increased IL-4 and IL-10 production in trophoblasts, and IL-10 production in DSCs. However, the coculture of trophoblasts with DSCs and DICs significantly increased interferon (IFN)-γ expression in DSCs, and tumor-necrosis factor (TNF)-α expression in DICs. No change was seen in Th1-type cytokine production in trophoblasts, and in Th2-type cytokine production in DICs in all cocultures. Furthermore, pre-treatment with anti-CXCR4 neutralizing antibody upregulated the production of the Th1-type cytokines IFN-γ and TNF-α, and downregulated the production of the Th2-type cytokines IL-4 and IL-10, in trophoblasts, DSCs, DICs or their cocultures. Interestingly, rhCXCL12 inhibited production of the Th1-type cytokine TNF-α and enhanced the expression of the Th2-type cytokines such as IL-4 and IL-10 in DICs; this effect was abrogated by anti-CXCR4 antibody. Our present study has elucidated the individual contributions of component cells to the shaping of Th2 bias, and uncovered a complicated cross-talk via the CXCL12/CXCR4 signal at the maternal/fetal interface in early human pregnancy.

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Acknowledgements

This work was supported by the Key Project and Major International Joint Research Project of NSFC 30730087, 30910103909, the Program for Outstanding Medical Academic Leader (all to DJ Li), NSFC 81070537, NSFC 31171437, the Shanghai PuJiang Talent Program 10PJ1401600 (all to MR Du) and the Natural Science Research Program for colleges and universities of Jiangsu Province 10KJB320021 (to R Zhu).

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Authors and Affiliations

  1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, 200011, China

    Hai-Lan Piao, Yu Tao, Rui Zhu, Song-Cun Wang, Chuan-Ling Tang, Qiang Fu, Mei-Rong Du & Da-Jin Li

  2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sochow University, Suzhou, 215006, China

    Rui Zhu

  3. Department of Immunology, Binzhou Medical University, Yantai, 264003, China

    Qiang Fu

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  1. Hai-Lan Piao
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Correspondence to Mei-Rong Du or Da-Jin Li.

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Piao, HL., Tao, Y., Zhu, R. et al. The CXCL12/CXCR4 axis is involved in the maintenance of Th2 bias at the maternal/fetal interface in early human pregnancy. Cell Mol Immunol 9, 423–430 (2012). https://doi.org/10.1038/cmi.2012.23

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