Interleukin-15 induces rapid tyrosine phosphorylation of STAT6 and the expression of interleukin-4 in mouse mast cells

Akio Masuda, Tetsuya Matsuguchi, Kenichi Yamaki, Tetsuo Hayakawa, Masato Kubo, William J. Larochelle, Yasunobu Yoshikai

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    53 Citations (Scopus)

    Abstract

    Interleukin (IL)-4 plays an important role in the differentiation of naive T helper (Th) cells into Th2. Mast cells can produce a significant amount of IL-4 and have been proposed to play a major role in the induction of Th2 responses. Recently, it has been reported that mast cells have a distinct IL-15 receptor system different from that of T or natural killer cells. In the present study, we demonstrated that IL-15 induced IL-4 production from a mouse mast cell line, MC/9, and bone marrow-derived mast cells. IL-4 mRNA expression was increased by IL-15, suggesting that IL-15 promotes IL-4 expression at the transcriptional level. In these mast cells, signal transducer and activator of transcription (STAT) 6 were rapidly tyrosine-phosphorylated in response to IL-15. In MC/9 cells, the expression of a C-terminally truncated dominant negative form of STAT6 significantly suppressed the IL-4 mRNA up-regulation by IL-15, suggesting that STAT6 activation is essential for the IL-15-mediated IL-4 production. Additionally, tyrosine phosphorylation of Tyk2 was rapidly increased by IL-15 treatment in this cell line. Altogether, our results suggest that IL-15 plays an important role in stimulating early IL-4 production in mast cells that may be responsible for the initiation of Th2 response.

    Original languageEnglish
    Pages (from-to)29331-29337
    Number of pages7
    JournalJournal of Biological Chemistry
    Volume275
    Issue number38
    DOIs
    Publication statusPublished - Sep 22 2000

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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