Fc receptor γ-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils

• Published in: Nature immunology Vol. 10; no. 2; pp. 214 - 222
• Main Authors: Taki, Shinsuke, Hida, Shigeaki, Yamasaki, Sho, Sakamoto, Yuzuru, Takamoto, Masaya, Obata, Kazushige, Takai, Toshiyuki, Karasuyama, Hajime, Sugane, Kazuo, Saito, Takashi
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2009; Nature Publishing Group
• Subjects: Animals; Basophils; Basophils - cytology; Basophils - immunology; Basophils - metabolism; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cell Differentiation - immunology; Cell Proliferation; Cell receptors; Flow Cytometry; Immunology; Immunoprecipitation; Infectious Diseases; Interleukin-3 - immunology; Interleukin-3 - metabolism; Interleukin-4 - biosynthesis; Interleukin-4 - immunology; Interleukins; Intracellular Signaling Peptides and Proteins - immunology; Intracellular Signaling Peptides and Proteins - metabolism; Mice; Mice, Transgenic; Physiological aspects; Protein-Tyrosine Kinases - immunology; Protein-Tyrosine Kinases - metabolism; Receptors, IgG - genetics; Receptors, IgG - immunology; Receptors, IgG - metabolism; Receptors, Interleukin-3 - immunology; Receptors, Interleukin-3 - metabolism; Signal Transduction - immunology; Syk Kinase; Th2 Cells - cytology; Th2 Cells - immunology; Transcriptional Activation - immunology; Japan
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.1686

The adaptor Fc receptor common γ-chain transduces signals for many immunoreceptors. Taki and colleagues find that this adaptor 'reroutes' interleukin 3 signals to induce interleukin 4 production and T helper 2 differentiation. The Fc receptor common γ-chain (FcRγ) is a widely expressed adaptor bearing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors. We show here that basophils lacking FcRγ developed normally and proliferated efficiently in response to interleukin 3 (IL-3) but were very impaired in IL-3-induced production of IL-4 and in supporting T helper type 2 differentiation. Through its transmembrane portion, FcRγ associated constitutively with the common β-chain of the IL-3 receptor and signaled by recruiting the kinase Syk. Retrovirus-mediated complementation demonstrated the essential function of the ITAM of FcRγ in IL-3 signal transduction. Our results identify a previously unknown mechanism whereby FcRγ functions to 'route' selective cytokine-triggered signals into the ITAM-mediated IL-4 production pathway.