INSERM UMR 1064, Nantes, France.
PLoS One. 2012;7(3):e33713. doi: 10.1371/journal.pone.0033713. Epub 2012 Mar 13.
Plasmacytoid dendritic cells (pDCs) are a subset of DCs whose major function relies on their capacity to produce large amount of type I IFN upon stimulation via TLR 7 and 9. This function is evolutionary conserved and place pDC in critical position in the innate immune response to virus. Here we show that rat pDC constitutively express TNF-related activation-induced cytokine (TRANCE) also known as Receptor-activating NF-κB ligand (RANKL). TRANCE/RANKL is a member of the TNF superfamily which plays a central role in osteoclastogenesis through its interaction with its receptor RANK. TRANCE/RANK interaction are also involved in lymphoid organogenesis as well as T cell/DC cross talk. Unlike conventional DC, rat CD4(high) pDC were shown to constitutively express TRANCE/RANKL both at the mRNA and the surface protein level. TRANCE/RANKL was also induced on the CD4(low) subsets of pDC following activation by CpG. The secreted form of TRANCE/RANKL was also produced by rat pDC. Of note, levels of mRNA, surface and secreted TRANCE/RANKL expression were similar to that observed for activated T cells. TRANCE/RANKL expression was found on pDC in all lymphoid organs as well blood and BM with a maximum expression in mesenteric lymph nodes. Despite this TRANCE/RANKL expression, we were unable to demonstrate in vitro osteoclastogenesis activity for rat pDC. Taken together, these data identifies pDC as novel source of TRANCE/RANKL in the immune system.
浆细胞样树突状细胞 (pDC) 是树突状细胞的一个亚群，其主要功能依赖于其在 TLR 7 和 9 刺激下产生大量 I 型 IFN 的能力。这种功能在进化上是保守的，使 pDC 在病毒固有免疫反应中处于关键地位。在这里，我们显示大鼠 pDC 持续表达 TNF 相关激活诱导细胞因子 (TRANCE)，也称为 NF-κB 配体激活受体 (RANKL)。TRANCE/RANKL 是 TNF 超家族的成员，通过与受体 RANK 相互作用，在破骨细胞生成中发挥核心作用。TRANCE/RANK 相互作用也参与淋巴器官发生以及 T 细胞/DC 相互作用。与传统的 DC 不同，大鼠 CD4(high) pDC 在 mRNA 和表面蛋白水平上均持续表达 TRANCE/RANKL。CpG 激活后，CD4(low) 亚群的 pDC 也诱导表达 TRANCE/RANKL。大鼠 pDC 还产生 TRANCE/RANKL 的分泌形式。值得注意的是，mRNA、表面和分泌的 TRANCE/RANKL 表达水平与激活的 T 细胞相似。TRANCE/RANKL 在所有淋巴器官以及血液和 BM 中的 pDC 上表达，在肠系膜淋巴结中表达最高。尽管存在这种 TRANCE/RANKL 表达，但我们无法在体外证明大鼠 pDC 的破骨细胞生成活性。总之，这些数据将 pDC 鉴定为免疫系统中 TRANCE/RANKL 的新来源。
