IL-4 Confers NK Stimulatory Capacity to Murine Dendritic Cells: A Signaling Pathway Involving KARAP/DAP12-Triggering Receptor Expressed on Myeloid Cell 2 Molecules

Magali Terme, Elena Tomasello, Koji Maruyama, Florent Crépineau, Nathalie Chaput, Caroline Flament, Jean Pierre Marolleau, Eric Angevin, Erwin F. Wagner, Benoît Salomon, François A. Lemonnier, Hiro Wakasugi, Marco Colonna, Eric Vivier, Laurence Zitvogel

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Dendritic cells (DC) regulate NK cell functions, but the signals required for the DC-mediated NK cell activation, i.e., DC-activated NK cell (DAK) activity, remain poorly understood. Upon acute inflammation mimicked by LPS or TNF-α, DC undergo a maturation process allowing T and NK cell activation in vitro. Chronic inflammation is controlled in part by Th2 cytokines. In this study, we show that IL-4 selectively confers to DC NK but not T cell stimulatory capacity. IL-4 is mandatory for mouse bone marrow-derived DC grown in GM-CSF (DCGM/IL-4) to promote NK cell activation in the draining lymph nodes. IL-4-mediated DAK activity depends on the KARAP/DAP12-triggering receptor expressed on myeloid cell 2 signaling pathway because: 1) gene targeting of the adaptor molecule KARAP/DAP12, a transmembrane polypeptide with an intracytoplasmic immunoreceptor tyrosine-based activation motif, suppresses the DCGM/IL-4 capacity to activate NK cells, and 2) IL-4-mediated DAK activity is significantly blocked by soluble triggering receptor expressed on myeloid cell 2 Fc molecules. These data outline a novel role for Th2 cytokines in the regulation of innate immune responses through triggering receptors expressed on myeloid cells.

Original languageEnglish
Pages (from-to)5957-5966
Number of pages10
JournalJournal of Immunology
Volume172
Issue number10
DOIs
StatePublished - May 15 2004

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