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

Shigeaki Hida; Sho Yamasaki; Yuzuru Sakamoto; Masaya Takamoto; Kazushige Obata; Toshiyuki Takai; Hajime Karasuyama; Kazuo Sugane; Takashi Saito; Shinsuke Taki

doi:10.1038/ni.1686

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

Shigeaki Hida, Sho Yamasaki, Yuzuru Sakamoto, Masaya Takamoto, Kazushige Obata, Toshiyuki Takai, Hajime Karasuyama, Kazuo Sugane, Takashi Saito, Shinsuke Taki

Division of Aging Science

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	214-222
Number of pages	9
Journal	Nature Immunology
Volume	10
Issue number	2
DOIs	https://doi.org/10.1038/ni.1686
Publication status	Published - 2009

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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

abstract = "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.",

author = "Shigeaki Hida and Sho Yamasaki and Yuzuru Sakamoto and Masaya Takamoto and Kazushige Obata and Toshiyuki Takai and Hajime Karasuyama and Kazuo Sugane and Takashi Saito and Shinsuke Taki",

note = "Funding Information: We thank S. Akira (Osaka University) for Stat6–/– mice; W.R. Heath (Walter and Eliza Hall Institute) for OT-II TCR-Tg mice; T. Kitamura (University of Tokyo) for the original pMX-IRES-GFP retroviral vector; and K. Takatsu (University of Toyama) for the Y16 cell line; and acknowledge the late N. Azuta for technical assistance. Supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Japan Society for the Promotion of Science (Grants-in-Aid for Scientific Research 17047016, 18060016 to S.T. and 19591162 to S.H.).",

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doi = "10.1038/ni.1686",

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AU - Hida, Shigeaki

AU - Yamasaki, Sho

AU - Sakamoto, Yuzuru

AU - Takamoto, Masaya

AU - Obata, Kazushige

AU - Takai, Toshiyuki

AU - Karasuyama, Hajime

AU - Sugane, Kazuo

AU - Saito, Takashi

AU - Taki, Shinsuke

N1 - Funding Information: We thank S. Akira (Osaka University) for Stat6–/– mice; W.R. Heath (Walter and Eliza Hall Institute) for OT-II TCR-Tg mice; T. Kitamura (University of Tokyo) for the original pMX-IRES-GFP retroviral vector; and K. Takatsu (University of Toyama) for the Y16 cell line; and acknowledge the late N. Azuta for technical assistance. Supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Japan Society for the Promotion of Science (Grants-in-Aid for Scientific Research 17047016, 18060016 to S.T. and 19591162 to S.H.).

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

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

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