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Blood, 15 September 2000, Vol. 96, No. 6, pp. 2172-2180
IMMUNOBIOLOGY
Role of common cytokine receptor  chain (c)-
and Jak3-dependent signaling in the proliferation and survival of
murine mast cells
Kotaro Suzuki,
Hiroshi Nakajima,
Norihiko Watanabe,
Shin-ichiro Kagami,
Akira Suto,
Yasushi Saito,
Takashi Saito, and
Itsuo Iwamoto
From the Department of Internal Medicine II, Chiba
University School of Medicine, Chiba; and Department of Molecular
Genetics, Chiba University Graduate School of Medicine, Chiba, Japan.
The regulatory roles of the common cytokine receptor  chain
(c)- and Jak3-dependent signaling in the proliferation
and survival of mast cells were determined using
c-deficient (c ) and
Jak3-deficient (Jak3) mice. Although the mast cells in
c and Jak3 mice were
morphologically indistinguishable from those in wild-type mice, the
number of peritoneal mast cells was decreased in
c and Jak3 mice as compared
with that in wild-type mice. Among c-related cytokines,
interleukin (IL)-4 and IL-9, but not IL-2, IL-7, or IL-15, enhanced the
proliferation and survival of bone marrow-derived mast cells (BMMCs)
from wild-type mice. However, the effects of IL-4 and IL-9 were absent
in BMMCs from c and Jak3
mice. In addition, IL-4R , c, and Jak3, but not
IL-2R or IL-7R, were expressed in BMMCs. In contrast, IL-13 did
not significantly induce the proliferation and survival of BMMCs even
from wild-type mice, and IL-13R1 was not expressed in BMMCs.
Furthermore, IL-4 phosphorylated the 65-kd isoform of Stat6 in BMMCs
from wild-type mice but not from c and
Jak3 mice. These results indicate that c-
and Jak3-dependent signaling is essential for IL-4- and IL-9-induced
proliferation and survival of murine mast cells, that the effects of
IL-4 are mediated by type I IL-4R and that type II IL-4R is absent on
mast cells, and that IL-4 phosphorylates the 65-kd isoform of Stat6 in
mast cells in a c- and Jak3-dependent manner.
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