Role of common cytokine receptor gamma chain (gamma(c))- and Jak3-dependent signaling in the proliferation and survival of murine mast cells

Citation
K. Suzuki et al., Role of common cytokine receptor gamma chain (gamma(c))- and Jak3-dependent signaling in the proliferation and survival of murine mast cells, BLOOD, 96(6), 2000, pp. 2172-2180
Citations number
63
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
0006-4971 → ACNP
Volume
96
Issue
6
Year of publication
2000
Pages
2172 - 2180
Database
ISI
SICI code
0006-4971(20000915)96:6<2172:ROCCRG>2.0.ZU;2-T
Abstract
The regulatory roles of the common cytokine receptor gamma chain (gamma(c)) - and Jak3-dependent signaling in the proliferation and survival of mast ce lls were determined using gamma(c)-deficient (gamma(c)(-)) and Jak3-deficie nt (Jak3(-)) mice. Although the mast cells in gamma(c)(-) and Jak3(-) mice were morphologically indistinguishable from those in wild-type mice, the nu mber of peritoneal mast cells was decreased in gamma(c)- and Jak3(-) mice a s compared with that in wild-type mice. Among gamma(c)-related cytokines, i nterleukin (IL)-4 and IL-9, but not IL-2, IL-7, or IL-15, enhanced the prol iferation 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 gamma(c)(-) and Jak3(-) mice. In addition, IL-4R alpha, gamma(c), and Jak3, but not IL-2R beta or IL-7R alpha, were expressed in BMMCs, In contrast, I L-13 did not significantly induce the proliferation and survival of BMMCs e ven from wild-type mice, and IL-13R alpha 1 was not expressed in BMMCs, Fur thermore, IL-4 phosphorylated the 65-kd isoform of Stat6 in BMMCs from wild -type mice but not from gamma(c)(-) and Jak3(-) mice. These results indicat e that gamma(c)- and Jak3-dependent signaling is essential for IL-4- and IL -9-induced proliferation and survival of murine mast cells, that the effect s 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 gamma(c)- and Jak3-dependent manner. (Blood, 2000;96:2172-2180) (C) 2000 by The American Society of Hematology.