Essential role of Stat6 in IL-4 signalling.
Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system. 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 4PS. 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 IgG1 responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses.
Takeda
K
K
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Tanaka
T
T
Shi
W
W
Matsumoto
M
M
Minami
M
M
Kashiwamura
S
S
Nakanishi
K
K
Yoshida
N
N
Kishimoto
T
T
Akira
S
S
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D018390:Gene Targeting; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007070:Immunoglobulin A / Q000096:biosynthesis; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009559:Nippostrongylus / Q000276:immunology; D017455:Receptors, IgE / Q000096:biosynthesis; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D000909:Antibodies, Helminth; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D017455:Receptors, IgE; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E