FcεIγ-ITAM Is Differentially Required for Mast Cell Function in Vivo

Daiju Sakurai, Sho Yamasaki, Kanako Arase, Seung Yong Park, Hisashi Arase, Akiyoshi Konno, Takashi Saito

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    Abstract

    The cross-linking of IgE-bound FcεRI by Ags triggers mast cell activation leading to allergic reactions. The in vivo contribution of FcγRIγ signaling to IgE/FcεRI-mediated mast cell responses has not yet been elucidated. In this study FcεRIγ-/- mast cells were reconstituted with either wild-type or mutant FcεRIγ in transgenic mice and transfected mast cells in vitro. We demonstrate that FcεRIγ-immunoreceptor tyrosine-based activation motif is essential for degranulation, cytokine production, and PG synthesis as well as for passive systemic anaphylaxis. Recent reports have suggested that cell surface FcεRI expression and mast cell survival are regulated by IgE in the absence of Ag, although the molecular mechanism is largely unknown. We also found that the promotion of mast cell survival by IgE without Ags is mediated by signals through the FcεRIγ-immunoreceptor tyrosine-based activation motif. In contrast, the IgE-mediated up-regulation of FcεRI is independent of FcεRIγ signaling. These results indicate that FcεRIγ-mediated signals differentially regulate the receptor expression, activation, and survival of mast cells and systemic anaphylaxis.

    Original languageEnglish
    Pages (from-to)2374-2381
    Number of pages8
    JournalJournal of Immunology
    Volume172
    Issue number4
    Publication statusPublished - Feb 15 2004

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    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Sakurai, D., Yamasaki, S., Arase, K., Park, S. Y., Arase, H., Konno, A., & Saito, T. (2004). FcεIγ-ITAM Is Differentially Required for Mast Cell Function in Vivo. Journal of Immunology, 172(4), 2374-2381.