A conceptual model for 5-HT uptake and release by DCs and the immunologic consequences. Immature DCs (iDC) may sequester 5-HT released by platelets or mast cells at sites of injury and inflammation, which they in turn secrete via a Ca²⁺-dependent exocytotic pathway on encountering naive, cognate T cells. High local concentrations of 5-HT within DC–T-cell synaptic junctions suppress further production of cAMP and facilitate T-cell proliferation. CD40-CD40 ligand signaling up-regulates DC SERT expression and thereby promotes uptake of 5-HT passively released from activated T cells. Mature DCs (mDC) may shuttle 5-HT between activated and naive T cells, thereby amplifying adaptive immune responses.