Rapid and large amount of autocrine IL-3 production is responsible for mast cell survival by IgE in the absence of antigen

Masayuki Kohno, Sho Yamasaki, Victor L.J. Tybulewicz, Takashi Saito

    Research output: Contribution to journalArticle

    62 Citations (Scopus)

    Abstract

    Cross-linking FceRI on mast cells by immunoglobulin E (IgE) and antigen (Ag) initiates cascades leading to antiparasitic or allergic responses. It was recently reported that IgE without antigen, IgE(-Ag), actively promotes mast cell survival. Although we have demonstrated that the immunoreceptor tyrosine-based activation motif within FcRγ is essential for IgE(-Ag)-induced mast cell survival, the underlying mechanism remains still unclear. Here, we investigated the mechanism of IgE(-Ag)-induced survival using mast cells lacking several downstream molecules. Lyn and Syk were essential, whereas Fyn, Gab2, and the phosphoinositide 3-kinase-Akt pathway were not critical for survival. Failure of survival in FcRγ-/- bone marrow mast cells (BMMCs) was rescued by coculture with IgE-treated wild-type BMMCs, suggesting that survival is induced not directly through FcεRI signals. We found that the survival is predominantly mediated by high production of interleukin 3 (IL-3), evidenced by severe impairment of survival by anti-IL-3 and in IL-3-/- BMMCs. The up-regulation of Bcl-xL/Bcl-2 by IgE was abrogated in IL-3-/- BMMCs, whereas the expression of histidine decarboxylase was normally induced. These results indicate that IL-3 plays a crucial role for IgE(-Ag)-induced mast cell survival, functioning in an autocrine manner by inducing the BclxL/Bcl-2 via signal transducer and activator of transduction 5. We further suggest that IgE(-Ag)-mediated gene expression in mast cells is regulated at least 2 mechanisms: autocrine IL-3 dependent and independent.

    Original languageEnglish
    Pages (from-to)2059-2065
    Number of pages7
    JournalBlood
    Volume105
    Issue number5
    DOIs
    Publication statusPublished - Mar 1 2005

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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