OX40L is expressed by many cell types, including antigen presenting cells (APCs), T cells, vascular endothelial cells, mast cells (MCs), and natural killer cells. The importance of OX40L:OX40 interactions and the OX40L signaling is crucial for the homeostasis and for the modulation of the effector functions of the immune system. However, the lack of non-murine/non-IgG commercially available OX40L-triggering antibodies and the potential signal cross-contamination caused by the binding to the FcγRs co-expressed by several immune cells have limited the study of the OX40L-signaling cascade. We recently characterized the functions and described the molecular events, which follow the engagement of OX40L in MCs, by the use of the soluble OX40 molecule, able to mimic the regulatory T cell-driven engagement of MC-OX40L. This molecule enables signaling studies in MCs with any requirement for OX40-expressing cells. Using this unique reagent, we determined the modality and the extent by which the engagement of OX40L in MCs influences the IgE-dependent MC degranulation. This tool may find a potential application for signaling studies of other OX40L-expressing populations other than MCs, mainly APCs, with similar approaches we reported for the study of OX40L cascade.
