The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells

Summary Interleukin-12 (IL-12), produced by dendritic cells in response to activation, is central to pathogen eradication and tumor rejection. The trafficking pathways controlling spatial distribution and intracellular transport of IL-12 vesicles to the cell surface are still unknown. Here, we show that intracellular IL-12 localizes in late endocytic vesicles marked by the SNARE VAMP7. Dendritic cells (DCs) from VAMP7-deficient mice are partially impaired in the multidirectional release of IL-12. Upon encounter with antigen-specific T cells, IL-12-containing vesicles rapidly redistribute at the immune synapse and release IL-12 in a process entirely dependent on VAMP7 expression. Consistently, acquisition of effector functions is reduced in T cells stimulated by VAMP7-null DCs. These results provide insights into IL-12 intracellular trafficking pathways and show that VAMP7-mediated release of IL-12 at the immune synapse is a mechanism to transmit innate signals to T cells.
Graphical Abstract
Highlights • Intracellular trafficking of IL-12 in dendritic cells is mediated by the SNARE VAMP7 • VAMP7 is required for optimal secretion of IL-12 in the extracellular space • IL-12/VAMP7+ vesicles gather at the immune synapse • VAMP7 controls synaptic release of IL-12 and IFN-γ production in T cells
Efficient priming of T cells requires antigenic and soluble cytokine signals. Chiaruttini et al. analyze the intracellular trafficking pathway of IL-12 in dendritic cells and identify the SNARE VAMP7 as a key regulator of cytokine release and T cell activation.