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 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.
Masuda
A
A
Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Matsuguchi
T
T
Yamaki
K
K
Hayakawa
T
T
Kubo
M
M
LaRochelle
W J
WJ
Yoshikai
Y
Y
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D019409:Interleukin-15 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D018418:Th2 Cells / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*; D014443:Tyrosine
D019409:Interleukin-15; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D014443:Tyrosine