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Essential role of Stat6 in IL-4 signalling.

Nature | Apr 18, 1996

http://www.ncbi.nlm.nih.gov/pubmed/8602263

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.

Pubmed ID: 8602263 RIS Download

Mesh terms: Animals | Antibodies, Helminth | B-Lymphocytes | Cell Line | Cells, Cultured | Cytokines | Gene Targeting | Histocompatibility Antigens Class II | Immunoglobulin A | Immunoglobulin Class Switching | Immunoglobulin E | Immunoglobulin G | Interleukin-4 | Lymphocyte Activation | Mice | Nippostrongylus | Receptors, IgE | STAT6 Transcription Factor | Signal Transduction | Spleen | T-Lymphocytes | T-Lymphocytes, Helper-Inducer | Trans-Activators

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