TRANCE is a TNF family member that regulates dendritic cell and osteoclast function

Tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) is a new member of the TNF family emerging as a key regulator of the immune system and of bone development and homeostasis. TRANCE is expressed on activated T cells and activates mature dendritic cells (DC), suggesting that it plays a role in the T cell-DC interaction during an immune response. Furthermore, TRANCE is expressed on osteoblasts stimulated with vitamin D3, dexamethasone, and parathyroid hormone. TRANCE, when expressed on osteoblasts, induces osteoclastogenesis and osteoclast activation, suggesting that it links known calciotropic hormones to bone resorption. TRANCE mediates its effects via the TRANCE-receptor (TRANCE-R/RANK), whereas its activity can be inhibited by the soluble decoy receptor osteoprotegerin/osteoclast inhibitory factor (OPG/OCIF). OPG can be neutralized by another TNF-family member, the TNF-related apoptosis-inducing ligand (TRAIL), suggesting that TRANCE is part of a complex cytokine network that regulates a diverse set of functions. We will discuss the current literature describing TRANCE and its receptors and its role in controlling DC and osteoclast function.