Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions

Evelyn Ullrich, Mathieu Bonmort, Gregoire Mignot, Benedikt Jacobs, Daniela Bosisio, Silvano Sozzani, Abdelali Jalil, Fawzia Louache, Elena Bulanova, Frederic Geissman, Bernard Ryffel, Nathalie Chaput, Silvia Bulfone-Paus, Laurence Zitvogel

Research output: Contribution to journalArticlepeer-review

Abstract

IFN-producing killer dendritic cells (IKDC) were initially described as B220 +CDllc +CD3 -NKl.l + tumor-infiltrating cells that mediated part of the antitumor effects of the combination therapy with imatinib mesylate and IL-2. In this study, we show their functional dependency on IL-15 during homeostasis and inflammatory processes. Trans-presentation of IL-15 by IL-15Rα allows dramatic expansion of IKDC in vitro and in vivo, licenses IKDC for TRAIL-dependent killing and endows IKDC with immunizing potential, all three biological attributes not shared by B220 -NK cells. However, IL-15 down-regulates the capacity of IKDC to induce MHC class I-or II-restricted T cell activation in vitro. Trans-presentation of IL-15 by IL-15Rα allows IKDC to respond to TLR3 and TLR4 ligands for the production of CCL2, a chemokine that is critical for IKDC trafficking into tumor beds (as described recently). We conclude that IKDC represent a unique subset of innate effectors functionally distinguishable from conventional NK cells in their ability to promptly respond to IL-15-driven inflammatory processes.

Original languageEnglish
Pages (from-to)7887-7897
Number of pages11
JournalJournal of Immunology
Volume180
Issue number12
Publication statusPublished - 2008

ASJC Scopus subject areas

  • Immunology

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