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Human trophoblast cells induced MDSCs from peripheral blood CD14+ myelomonocytic cells via elevated levels of CCL2

Cellular & Molecular Immunology volume 13, pages 615–627 (2016)Cite this article

Abstract

Successful human pregnancy requires the maternal immune system to recognize and tolerate the semi-allogeneic fetus. Myeloid-derived suppressor cells (MDSCs), which are capable of inhibiting T-cell responses, are highly increased in the early stages of pregnancy. Although recent reports indicate a role for MDSCs in fetal–maternal tolerance, little is known about the expansion of MDSCs during pregnancy. In the present study, we demonstrated that the trophoblast cell line HTR8/SVneo could instruct peripheral CD14+ myelomonocytic cells toward a novel subpopulation of MDSCs, denoted as CD14+HLA-DR−/low cells, with suppressive activity and increased expression of IDO1, ARG-1, and COX2. After interaction with HTR8/SVneo cells, CD14+ myelomonocytic cells secrete high levels of CCL2, promoting the expression of signal transducer and activator of transcription 3. We utilized a neutralizing monoclonal antibody to reveal the prominent role of CCL2 in the induction of CD14+HLA-DR−/low MDSCs. In combination, the results of the present study support a novel role for the cross-talk between the trophoblast cell line HTR8/SVneo and maternal CD14+ myelomonocytic cells in initiating MDSCs induction, prompting a tolerogenic immune response to ensure a successful pregnancy.

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Acknowledgements

We are very grateful to Dr Charles H. Graham (Department of Anatomy and Cell Biology, Queen's University, Kingston, ON, Canada) for providing the HTR8/SVneo cell line. This study was supported by grants from the National Natural Science Foundation of China (grant nos. 31470885, 31270971, 81300510, 31300752, and 31100650).

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  1. Xun Qu, (quxun@sdu.edu.cn)

Authors and Affiliations

  1. Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, People's Republic of China

    Yun Zhang, Jintang Sun, Lei Zhao, Qingjie Wang, Qianqian Shao & Xun Qu

  2. Institute of Stomatology, Qilu Hospital, Shandong University, Shandong, Jinan, 250012, Peoples's Republic of China

    Yun Zhang

  3. Department of Gynaecology and Obstetrics, Qilu Hospital of Shandong University, Shandong, Jinan, 250012, People's Republic of China

    Daiwei Qu & Beihua Kong

  4. The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong, Jinan, 250012, People's Republic of China

    Yun Zhang

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Supplementary Information accompanies the paper on Cellular & Molecular Immunology’s website (http://www.nature.com/cmi).

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Zhang, Y., Qu, D., Sun, J. et al. Human trophoblast cells induced MDSCs from peripheral blood CD14+ myelomonocytic cells via elevated levels of CCL2. Cell Mol Immunol 13, 615–627 (2016). https://doi.org/10.1038/cmi.2015.41

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