title: Human trophoblast cells induced MDSCs from peripheral blood CD14(+) myelomonocytic cells via elevated levels of CCL2.
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.
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.|Institute of Stomatology, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, Peoples's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gynaecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Daiwei
authors.initials: D
authors.lastname: Qu
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Department of Gynaecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
authors.affiliation: The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
mesh_terms: D049109:Cell Proliferation; D002469:Cell Separation; D018932:Chemokine CCL2 / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D018932:Chemokine CCL2; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D050796:STAT3 Transcription Factor