Wang Huijuan, He Min, Hou Yunhua, Chen Saiying, Zhang Xiaojie, Zhang Mingshun, Ji Xiaohui
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 210029, China; Department of Immunology, Nanjing Medical University, Nanjing, 210029, China.
Department of Immunology, Nanjing Medical University, Nanjing, 210029, China.
Placenta. 2016 Feb;38:76-83. doi: 10.1016/j.placenta.2015.12.001. Epub 2015 Dec 10.
Decidual macrophages (dMΦs) have been implicated in fetal tolerance, but little information is known regarding their differentiation capacity and interactions with T cells. The present study aimed to investigate the immunological characteristics of dMΦs at mid and term pregnancy.
The dMΦs were analyzed for their phenotypes and cytokine production by flow cytometry and ELISA, respectively. The transendothelial trafficking model was implemented to allow the dMΦs to differentiate. The differentiated cells from dMΦs were also measured for their phenotypes and cytokine production with same methods. The capacity of dMΦs or the differentiated cells from dMΦs to stimulate allogeneic T lymphocyte proliferation was evaluated by T lymphocyte stimulation assays. T cell differentiation was determined by flow cytometry.
The dMΦs in the mid-pregnancy (Mid-dMΦs) resembled the M2 phenotype. The differentiated cells from Mid-dMΦs had little stimulatory capacity on T cell proliferation and favored regulatory T cell differentiation. The dMΦs at term differentiated into dendritic (DC)-like cells, stimulating T cell activation, proliferation, and differentiation into IFN-γ-producing T cellsdecidual
The present study suggests that the differences in phenotypes and cytokine production between Mid- and Term-dMΦs relate to their different roles in the homeostasis of the maternal-fetal interface. Mid-dMΦs differentiate into DC-like cells with immunosuppressive properties, playing an important role in maintaining homeostasis required for a successful pregnancy. Term-dMΦs differentiate into DC-like cells with immunostimulatory properties, likely involved in the activation of labor. The different differentiation capacities of dMΦs in the varied pregnancy stages may be due to the placental microenvironment.
蜕膜巨噬细胞(dMΦs)与胎儿耐受性有关,但其分化能力以及与T细胞的相互作用尚不清楚。本研究旨在探讨妊娠中期和晚期dMΦs的免疫学特征。
分别采用流式细胞术和酶联免疫吸附测定法分析dMΦs的表型和细胞因子产生情况。采用跨内皮迁移模型使dMΦs分化。对dMΦs分化后的细胞也用相同方法检测其表型和细胞因子产生情况。通过T淋巴细胞刺激试验评估dMΦs或其分化细胞刺激同种异体T淋巴细胞增殖的能力。通过流式细胞术测定T细胞分化情况。
妊娠中期的dMΦs(Mid-dMΦs)类似M2表型。Mid-dMΦs分化后的细胞对T细胞增殖的刺激能力较弱,且有利于调节性T细胞分化。足月时的dMΦs分化为树突状(DC)样细胞,刺激T细胞活化、增殖并分化为产生γ干扰素的T细胞。
本研究表明,妊娠中期和晚期dMΦs在表型和细胞因子产生方面的差异与其在母胎界面稳态中的不同作用有关。妊娠中期的dMΦs分化为具有免疫抑制特性的DC样细胞,在维持成功妊娠所需的稳态中起重要作用。足月时的dMΦs分化为具有免疫刺激特性的DC样细胞,可能参与分娩的启动。不同妊娠阶段dMΦs的不同分化能力可能归因于胎盘微环境。