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.