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

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 o f 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 I L-15 receptor system different from that of T or natural killer cells. In t he 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 expr ession at the transcriptional Level. In these mast cells, signal transducer and activator of transcription (STAT) 6 were rapidly tyrosine-phosphorylat ed in response to IL-15. In MC/9 cells, the expression of a C-terminally tr uncated dominant negative form of STAT6 significantly suppressed the IL-4 m RNA up-regulation by IL-15, suggesting that STAT6 activation is essential f or the IL-15-mediated IL-4 production. Additionally, tyrosine phosphorylati on of Tyk2 was rapidly increased by IL-15 treatment in this cell line. Alto gether, our results suggest that IL-15 plays an important role in stimulati ng early IL-4 production in mast cells that may be responsible for the init iation of Th2 response.