We recently reported that human dendritic cells release the leaderless secretory protein interleukin-1β (IL-1β) following specific interaction with alloreactive T lymphocytes. To clarify the molecular mechanism underlying this secretion, this study investigated the intracellular trafficking of IL-1β in dendritic cells and the signal(s) regulating its release. Results show that a fraction of the intracellular IL-1β precursor colocalizes with the hydrolase cathepsin D in endolysosomes of dendritic cells; secretion of both proteins is elicited by stimuli that induce intracellular calcium increases. Alloreactive CD8+ T lymphocytes generate a Ca++ influx in dendritic cells followed by enrichment in endolysosomes containing IL-1β and cathepsin D beneath the membrane in contact with T cells. These events result in polarized exocytosis of secretory lysosomes, mediated by microtubules, with release of IL-1β and cathepsin D toward the interacting CD8+ T cell.
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