Naranjo-Gómez Mar, Oliva Harold, Climent Nuria, Fernández Marco A, Ruiz-Riol Marta, Bofill Margarita, Gatell José M, Gallart Teresa, Pujol-Borrell Ricardo, Borràs Francesc E
Laboratory of Immunobiology for Research and Applications to Diagnosis, Blood and Tissue Bank, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
Eur J Immunol. 2007 Jul;37(7):1764-72. doi: 10.1002/eji.200636980.
Human and mouse plasmacytoid dendritic cells (PDC) express IL-2 mRNA specifically upon TLR stimulation, but not under CD40L stimulation. Even though the expression of the IL-2R by PDC has been described, the functional implications of this expression remain unknown. Here, we investigated the expression and function of the IL-2R in activated human PDC. The IL-2Ralpha chain, CD25, is expressed in both CpG- and CD40L-activated PDC. CD25 expression is a relatively rapid event, as the receptor was detected 6 h after the initial activation signal. Exogenous IL-2 added to CD40L-activated PDC increased the expression of CD25, enhanced the secretion of pro-inflammatory cytokines and promotes PDC survival. CpG-activated PDC cultured in the presence of IL-2R-blocking monoclonal antibodies showed a reduced expression of pro-inflammatory cytokines, especially TNF-alpha. This reduction was dose and time dependent, suggesting a regulatory role of IL-2 in TNF secretion that might occur at the post-transcriptional level. These results indicate that the expression of the IL-2R is relevant to human PDC activation, and that IL-2 may be an important auto- and/or paracrine factor modulating the activation and survival of PDC. Finally, CD25 expression may be considered as a useful early activation marker for human PDC.
人和小鼠浆细胞样树突状细胞(pDC)在受到Toll样受体(TLR)刺激时特异性表达白细胞介素-2(IL-2)信使核糖核酸(mRNA),但在受到CD40配体(CD40L)刺激时则不表达。尽管已经报道了pDC表达IL-2受体(IL-2R),但其表达的功能意义仍不清楚。在此,我们研究了活化的人pDC中IL-2R的表达和功能。IL-2Rα链,即CD25,在经CpG和CD40L活化的pDC中均有表达。CD25的表达是一个相对快速的事件,因为在初始激活信号后6小时就能检测到该受体。添加到经CD40L活化的pDC中的外源性IL-2增加了CD25的表达,增强了促炎细胞因子的分泌并促进了pDC的存活。在存在IL-2R阻断单克隆抗体的情况下培养的经CpG活化的pDC显示促炎细胞因子的表达降低,尤其是肿瘤坏死因子-α(TNF-α)。这种降低呈剂量和时间依赖性,表明IL-2在TNF分泌中可能在转录后水平发挥调节作用。这些结果表明IL-2R的表达与人pDC的活化相关,并且IL-2可能是调节pDC活化和存活的重要自分泌和/或旁分泌因子。最后,CD25的表达可被视为人类pDC有用的早期活化标志物。