Abstract
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 CD4high pDC were shown to constitutively express TRANCE/RANKL both at the mRNA and the surface protein level. TRANCE/RANKL was also induced on the CD4low 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.
Highlights
Dendritic cells (DC), as antigen presenting cells (APC), play a key role in the induction of adaptive immunity [1]
Among the genes expressed in resting Plasmacytoid dendritic cells (pDCs), we identified TNF-related activationinduced cytokine (TRANCE)
We confirmed these data using real time QPCR (Fig. 1A) and observed that the level of TRANCE mRNA expression in resting pDC was similar to that observed at the peak of expression in activated T cells which are known to strongly expressed TRANCE [24]
Summary
Dendritic cells (DC), as antigen presenting cells (APC), play a key role in the induction of adaptive immunity [1]. Several DC subsets with specific phenotype and function have been described in human and mouse model [2,3]. PDC have been first described as plasmacytoid monocytes and plasmacytoid T cells [4]). They were described as DC in the 1990s [5], and were shown to be the natural IFN-producing cells [6]. PDC subsets with different phenotype and function have been recently described. CD2+ and CD22 pDC have been described with CD2+ pDC exhibiting an in vitro cytotoxic activity and expression of lysozyme [9]. A subset of CCR9+ pDC was recently shown to exhibit tolerogenic functions [12]
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