可诱导共刺激分子诱导骨髓来源不成熟树突状细胞特异性分泌IL-6

ICOS/ICOSL-dependent production of IL-6 in mouse bone-marrow derived immature dendritic cells

目的:分析可诱导共刺激分子(ICOS)可溶性融合蛋白(ICOSIg)能否向不成熟DCs传递逆向信号及其性质。方法:以流式细胞仪结合特异性抗体检测DCs表型分子改变;以ELISA检测培养上清细胞因子变化;以RT-PCR检测各组DCs细胞内细胞因子及受体、趋化因子等mRNA表达水平。结果:ICOSIg或膜锚定ICOS作用于不成熟DCs,均可诱导其高表达MHC-Ⅱ、CD80、CD86和CD83等表型分子;促进DCs特异性分泌IL-6。结论:ICOS作用于不成熟DCs表面的ICOSL可以向DCs细胞传递逆向信号,诱导DCs细胞高分泌IL-6,同时其表面重要的表型分子也上调,可能参与了DCs细胞免疫功能的调节,其信号转导机制可能涉及p38-MAPK通路。

Objective：To determine whether ICOS could deliver any reverse signals through ICOSL expressed on mouse-derived immature dendritic cells（DCs） and to detail their possible characteristics.Methods：The surface phenotype molecules of DCs were determined by flow cytometry and the variation of cytokines was detected by ELISA.Real-time PCR was used for the evaluation of mRNA levels of cytokines,chemokines and their receptors.Results：High expression of MHC-Ⅱ,CD80,CD86 and CD83 was induced on the surface of DCs when they were coincubated with ICOSIg or CHO cells expressing membrane-anchored ICOS.More intriguingly,IL-6 was significantly and specifically elevated in these conditions.Conclusion：Our data,for the first time,provide some biological proofs showing that ICOS,through binding ICOSL on the cell surface,can deliver some reverse signals to immature DCs,inducing a specific secretion of IL-6 by activating p38-MAPK signal pathway.