IL-4 confers NK stimulatory capacity to murine dendritic cells: a signaling pathway involving KARAP/DAP12-triggering receptor expressed on myeloid cell 2 molecules.

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-alpha, 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 (DC(GM/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 DC(GM/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.

• Authors: 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
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 172 Issue 10 Pg. 5957-66 (May 15 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15128777 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Adaptor Proteins, Vesicular Transport
• Lipopolysaccharides
• Membrane Glycoproteins
• Receptors, Immunologic
• Trem2 protein, mouse
• Tumor Necrosis Factor-alpha
• Tyrobp protein, mouse
• Interleukin-4

Topics

• Adaptor Proteins, Signal Transducing
• Adaptor Proteins, Vesicular Transport (biosynthesis, physiology)
• Adoptive Transfer
• Animals
• Cell Communication (genetics, immunology)
• Cells, Cultured
• Coculture Techniques
• Cytotoxicity, Immunologic (genetics, immunology)
• Dendritic Cells (immunology, metabolism, transplantation)
• Female
• Inflammation (genetics, immunology)
• Interleukin-4 (physiology)
• Killer Cells, Natural (immunology, metabolism)
• Lipopolysaccharides (pharmacology)
• Lymphocyte Activation (genetics, immunology)
• Membrane Glycoproteins (genetics, physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Nude
• Mice, SCID
• Receptors, Immunologic (biosynthesis, genetics, physiology)
• Signal Transduction (genetics, immunology)
• Tumor Necrosis Factor-alpha (pharmacology)