TRANCE counteracts FasL-mediated apoptosis of murine bone marrow-derived dendritic cells

Abstract

Dendritic cells (DCs) are the most potent APCs known to date. Despite their potency, DCs are short-lived. During the course of an immune response, DCs interact with cognate T cells, which upon activation express both DC survival and pro-apoptotic factors. This raises the question how DC longevity is regulated by these signals. In this study, we have assessed the roles of FasL (CD95L) and tumor necrosis factor-related activation-induced cytokine (TRANCE) in regulating the survival of murine bone marrow-derived DCs (BMDCs). We have shown for the first time that TRANCE protects DCs from FasL-mediated apoptosis, and that the quantitative balance between TRANCE and FasL can modulate BMDC survival in vitro. In addition, by quantifying adoptively transferred BMDCs in draining lymph nodes (LNs), we have shown that treating DCs with FasL prior to the transfer decreases the quantity of donor DCs capable of migrating to the LN, presumably due to FasL-mediated apoptosis of donor DCs in vivo. Furthermore, we have shown that TRANCE can counteract FasL and reverse such decrease. Taken together, these results suggest that the interplay between FasL and TRANCE play a role in regulating the survival of DCs.