Essential role of Stat6 in IL-4 signalling

K Takeda, T Tanaka, W Shi, M Matsumoto, M Minami… - Nature, 1996 - nature.com
K Takeda, T Tanaka, W Shi, M Matsumoto, M Minami, S Kashiwamura, K Nakanishi…
Nature, 1996nature.com
Abstract INTERLEUKIN-4 (IL-4) is a pleiotropic lymphokine which plays an important role in
the immune system1. IL-4 activates two distinct signalling pathways through tyrosine
phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K
protein called 4PS2–7. To investigate the functional role of Stat6 in IL-4 signalling, we
generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice,
expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells …
Abstract
INTERLEUKIN-4(IL-4) is a pleiotropic lymphokine which plays an important role in the immune system1. IL-4 activates two distinct signalling pathways through tyrosine phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K protein called 4PS2–7. To investigate the functional role of Stat6 in IL-4 signalling, we generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells was not enhanced in response to IL-4. IL-4-induced B-cell proliferation costimulated by anti-IgM antibody was abolished. The T-cell proliferative response was also notably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgGl responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4-deficient mice8,9 or using antibodies to IL-410 and the IL-4 receptor11. We conclude that Stat6 plays a central role in exerting IL-4-mediated biological responses.
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