Zhang Yuan, Wang Ying, Li Ming-Qing, Duan Jie, Fan Deng-Xuan, Jin Li-Ping
Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai Medical College, Shanghai 200011, P.R. China.
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Exp Ther Med. 2018 Feb;15(2):1855-1862. doi: 10.3892/etm.2017.5638. Epub 2017 Dec 15.
Decidual immune cells (DICs), consisting of both innate and adaptive immune cells, have a pivotal role in maintaining immune tolerance for normal pregnancy. Our previous study demonstrated that interleukin (IL)-25 stimulates the proliferation of decidual stromal cells (DSCs) in an autocrine manner. However, the role of IL-25 in functional regulation of DICs is largely unknown. Flow cytometry was used to analyze the expression of IL-25 and its receptor (IL-17RB) in DICs, and the effect of IL-25 on the expression of Ki-67, IL-4, IL-10, interferon (IFN)-γ and transforming growth factor (TGF)-β in decidual γδT cells. In addition, ELISA assays were performed to detect the secretion of IL-10 and TGF-β in decidual γδT cells. The present findings indicated that decidual CD56 bright CD16-natural killer (NK) cells, natural killer T (NKT) cells, regulatory T (Treg) cells, CD3 T cells, macrophages and γδT cells co-expressed IL-25 and IL-17RB, particularly γδT cells. Recombinant human (rh) IL-25 protein upregulated the expression of Ki-67, IL-4, and IL-10, but downregulated the expression of IFN-γ in γδT cells; however, anti-human IL-25 or IL-17RB neutralizing antibody reversed these effects. These data suggest that IL-25 may promote IL-10 production by γδT cells as well as the proliferation of γδT cells, and possibly forms a positive feedback loop to maintain a T helper 2 cell bias at the maternal-fetal interface and further contributes to the maintenance of successful pregnancy.
蜕膜免疫细胞（DICs）由先天性和适应性免疫细胞组成，在维持正常妊娠的免疫耐受中起关键作用。我们之前的研究表明，白细胞介素（IL）-25以自分泌方式刺激蜕膜基质细胞（DSCs）的增殖。然而，IL-25在DICs功能调节中的作用在很大程度上尚不清楚。采用流式细胞术分析IL-25及其受体（IL-17RB）在DICs中的表达，以及IL-25对蜕膜γδT细胞中Ki-67、IL-4、IL-10、干扰素（IFN）-γ和转化生长因子（TGF）-β表达的影响。此外，进行酶联免疫吸附测定（ELISA）以检测蜕膜γδT细胞中IL-10和TGF-β的分泌。目前的研究结果表明，蜕膜CD56亮CD16阴性自然杀伤（NK）细胞、自然杀伤T（NKT）细胞、调节性T（Treg）细胞、CD3 T细胞、巨噬细胞和γδT细胞共表达IL-25和IL-17RB，尤其是γδT细胞。重组人（rh）IL-25蛋白上调γδT细胞中Ki-67、IL-4和IL-10的表达，但下调IFN-γ的表达；然而，抗人IL-25或IL-17RB中和抗体可逆转这些作用。这些数据表明，IL-25可能促进γδT细胞产生IL-10以及γδT细胞的增殖，并可能形成正反馈回路，以维持母胎界面处的辅助性T细胞2型偏向，进而有助于维持成功妊娠。
