Zhao Lei, Shao Qianqian, Zhang Yun, Zhang Lin, He Ying, Wang Lijie, Kong Beihua, Qu Xun
Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, P.R. China.
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, P.R. China.
Sci Rep. 2016 Feb 9;6:20409. doi: 10.1038/srep20409.
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.
成功妊娠需要母体免疫适应以避免胎儿 - 胎盘单位被排斥。蜕膜微环境中的树突状细胞呈现出致耐受性特征。然而，这些致耐受性树突状细胞是如何被诱导的以及潜在机制在很大程度上尚不清楚。在本研究中，我们表明人绒毛外滋养层细胞可重定向单核细胞向树突状细胞的转变并诱导调节性树突状细胞。在人绒毛外滋养层细胞系HTR - 8/SVneo存在的情况下，从血液单核细胞分化而来的树突状细胞呈现出DC - SIGN(+)CD14(+)CD1a(-)表型，与蜕膜树突状细胞相似。经HTR8处理的树突状细胞在受到脂多糖刺激时无法发育出完全成熟的表型，并且显著改变了细胞因子分泌谱。在功能上，经处理的树突状细胞诱导同种异体T细胞增殖和活化的能力较差，而促进了CD4(+)CD25(+)Foxp3(+)调节性T细胞的生成。此外，树突状细胞与HTR - 8/SVneo共培养系统的上清液中含有大量的巨噬细胞集落刺激因子（M - CSF）和单核细胞趋化蛋白 - 1（MCP - 1）。我们使用中和抗体探讨了M - CSF和MCP - 1在绒毛外滋养层细胞介导的单核细胞向树突状细胞分化过程中的作用。我们的数据表明，人绒毛外滋养层细胞通过M - CSF和MCP - 1在调节单核细胞向树突状细胞分化中起重要作用，这有助于在母胎界面建立致耐受性微环境。
