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 journalArticle

43 Citations (Scopus)

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

Fingerprint

Interleukin-15
Dendritic Cells
Natural Killer Cells
Chemokine CCL2
Licensure
Interleukin-2
Neoplasms
Homeostasis
Down-Regulation
Ligands
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Ullrich, E., Bonmort, M., Mignot, G., Jacobs, B., Bosisio, D., Sozzani, S., ... Zitvogel, L. (2008). Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions. Journal of Immunology, 180(12), 7887-7897.

Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions. / Ullrich, Evelyn; Bonmort, Mathieu; Mignot, Gregoire; Jacobs, Benedikt; Bosisio, Daniela; Sozzani, Silvano; Jalil, Abdelali; Louache, Fawzia; Bulanova, Elena; Geissman, Frederic; Ryffel, Bernard; Chaput, Nathalie; Bulfone-Paus, Silvia; Zitvogel, Laurence.

In: Journal of Immunology, Vol. 180, No. 12, 2008, p. 7887-7897.

Research output: Contribution to journalArticle

Ullrich, E, Bonmort, M, Mignot, G, Jacobs, B, Bosisio, D, Sozzani, S, Jalil, A, Louache, F, Bulanova, E, Geissman, F, Ryffel, B, Chaput, N, Bulfone-Paus, S & Zitvogel, L 2008, 'Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions', Journal of Immunology, vol. 180, no. 12, pp. 7887-7897.
Ullrich E, Bonmort M, Mignot G, Jacobs B, Bosisio D, Sozzani S et al. Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions. Journal of Immunology. 2008;180(12):7887-7897.
Ullrich, Evelyn ; Bonmort, Mathieu ; Mignot, Gregoire ; Jacobs, Benedikt ; Bosisio, Daniela ; Sozzani, Silvano ; Jalil, Abdelali ; Louache, Fawzia ; Bulanova, Elena ; Geissman, Frederic ; Ryffel, Bernard ; Chaput, Nathalie ; Bulfone-Paus, Silvia ; Zitvogel, Laurence. / Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions. In: Journal of Immunology. 2008 ; Vol. 180, No. 12. pp. 7887-7897.
@article{b6b0ef97332e4766abefc41e239c4fa4,
title = "Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions",
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.",
author = "Evelyn Ullrich and Mathieu Bonmort and Gregoire Mignot and Benedikt Jacobs and Daniela Bosisio and Silvano Sozzani and Abdelali Jalil and Fawzia Louache and Elena Bulanova and Frederic Geissman and Bernard Ryffel and Nathalie Chaput and Silvia Bulfone-Paus and Laurence Zitvogel",
year = "2008",
language = "English",
volume = "180",
pages = "7887--7897",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

TY - JOUR

T1 - Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions

AU - Ullrich, Evelyn

AU - Bonmort, Mathieu

AU - Mignot, Gregoire

AU - Jacobs, Benedikt

AU - Bosisio, Daniela

AU - Sozzani, Silvano

AU - Jalil, Abdelali

AU - Louache, Fawzia

AU - Bulanova, Elena

AU - Geissman, Frederic

AU - Ryffel, Bernard

AU - Chaput, Nathalie

AU - Bulfone-Paus, Silvia

AU - Zitvogel, Laurence

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=50849131938&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50849131938&partnerID=8YFLogxK

M3 - Article

VL - 180

SP - 7887

EP - 7897

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -