Xu Fenghuang, Yi Junzhu, Wang Zhuoya, Hu Yejia, Han Chunlei, Xue Qun, Zhang Xueguang, Luan Xiying
Department of Immunology, Binzhou Medical University, Yantai, Shandong Province, 264003, People's Republic of China.
Department of Pathophysiology, Binzhou Medical University, Yantai, Shandong Province, 264003, People's Republic of China.
Immunol Res. 2017 Aug;65(4):903-912. doi: 10.1007/s12026-017-8929-8.
Interleukin 27 (IL-27) regulates T cell function and is involved in inflammation. It has been reported that human placenta-derived mesenchymal stromal cells (hPMSCs) can inhibit T cell responses and attenuate inflammation reactions. However, it is unclear whether IL-27 can regulate hPMSC function. Here, we examined the effects of IL-27 upon adherence, migration, and proliferation as well as the immunomodulatory effects of hPMSCs. The results show that IL-27 receptor α chain (IL-27Rα) is expressed in hPMSCs. IL-27 at 30 ng/ml inhibited hPMSC adherence and proliferation, while the migration of hPMSCs was promoted with IL-27 at doses of 20 or 30 ng/ml, as determined with use of real-time cell analysis (RTCA). Moreover, IL-27 promoted regulatory effects of hPMSCs through enhancing Th2 and suppressing Th1 subset generation from activated T cells in human peripheral blood. IL-27 also enhanced the ability of hPMSCs to secrete IL-10 from CD4T cells through increased expression levels of the programmed death ligand 1 (PDL1) in hPMSCs via the Janus kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) signaling pathway. In conclusion, IL-27 has significant modulatory effects on adherence, proliferation, and migration of hPMSCs. IL-27 increased PDL1 expression levels in hPMSCs via the JAK/STAT1 pathway, which then enhanced the regulatory effects of hPMSCs upon Th1 and Th2 cell generations and IL-10 secretion from CD4T cells.
白细胞介素27(IL-27)调节T细胞功能并参与炎症反应。据报道,人胎盘来源的间充质基质细胞(hPMSCs)可抑制T细胞反应并减轻炎症反应。然而,尚不清楚IL-27是否能调节hPMSC的功能。在此,我们研究了IL-27对hPMSC黏附、迁移和增殖的影响以及hPMSC的免疫调节作用。结果显示,hPMSCs表达IL-27受体α链(IL-27Rα)。使用实时细胞分析(RTCA)测定,30 ng/ml的IL-27抑制hPMSC的黏附和增殖,而20或30 ng/ml的IL-27促进hPMSC的迁移。此外,IL-27通过增强Th2细胞并抑制人外周血中活化T细胞产生Th1亚群,促进hPMSC的调节作用。IL-27还通过Janus激酶(JAK)/信号转导和转录激活因子1(STAT1)信号通路增加hPMSCs中程序性死亡配体1(PDL1)的表达水平,从而增强hPMSCs从CD4T细胞分泌IL-10的能力。总之,IL-27对hPMSC的黏附、增殖和迁移具有显著的调节作用。IL-27通过JAK/STAT1途径增加hPMSCs中PDL1的表达水平,进而增强hPMSCs对Th1和Th2细胞生成以及CD4T细胞分泌IL-10的调节作用。