title: Human monocytes undergo functional re-programming during differentiation to dendritic cell mediated by human extravillous trophoblasts.
abstract: Maternal immune adaptation is required for a successful pregnancy to avoid rejection of the fetal-placental unit. Dendritic cells within the decidual microenvironment lock in a tolerogenic profile. However, how these tolerogenic DCs are induced and the underlying mechanisms are largely unknown. In this study, we show that human extravillous trophoblasts redirect the monocyte-to-DC transition and induce regulatory dendritic cells. DCs differentiated from blood monocytes in the presence of human extravillous trophoblast cell line HTR-8/SVneo displayed a DC-SIGN(+)CD14(+)CD1a(-) phenotype, similar with decidual DCs. HTR8-conditioned DCs were unable to develop a fully mature phenotype in response to LPS, and altered the cytokine secretory profile significantly. Functionally, conditioned DCs poorly induced the proliferation and activation of allogeneic T cells, whereas promoted CD4(+)CD25(+)Foxp3(+) Treg cells generation. Furthermore, the supernatant from DC and HTR-8/SVneo coculture system contained significant high amount of M-CSF and MCP-1. Using neutralizing antibodies, we discussed the role of M-CSF and MCP-1 during monocyte-to-DCs differentiation mediated by extravillous trophoblasts. Our data indicate that human extravillous trophoblasts play an important role in modulating the monocyte-to-DC differentiation through M-CSF and MCP-1, which facilitate the establishment of a tolerogenic microenvironment at the maternal-fetal interface.
authors: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, P.R. China.
authors: Lei
authors: L
authors: Zhao
authors: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, P.R. China.
authors: Qianqian
authors: Q
authors: Shao
authors: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, P.R. China.
authors: Yun
authors: Y
authors: Zhang
authors: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, P.R. China.
authors: Lin
authors: L
authors: Zhang
authors: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, P.R. China.
authors: Ying
authors: Y
authors: He
authors: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, P.R. China.
authors: Lijie
authors: L
authors: Wang
authors: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, P.R. China.
authors: Beihua
authors: B
authors: Kong
authors: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, P.R. China.
authors: Xun
authors: X
authors: Qu
mesh_terms: D002460:Cell Line; D065150:Cellular Reprogramming / Q000187:drug effects / Q000276:immunology*; D018932:Chemokine CCL2 / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor