ESSENTIAL ROLE OF STAT6 IN IL-4 SIGNALING

Interleukin-4(IL-4) is a pleiotropic lymphokine which plays an importa nt role in the immune system(1). IL-4 activates two distinct signallin g pathways through tyrosine phosphorylation of Stat6, a signal transdu cer and activator of transcription, and of a 170K protein called 4PS(2 -7). To investigate the functional role of Stat6 in IL-4 signalling, w e generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibili ty complex (MHC) class II in resting B cells was not enhanced in respo nse to IL-4. IL-4-induced B-cell proliferation costimulated by anti-Ig M antibody was abolished. The T-cell proliferative response was also n otably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgG1 responses after nematode infection were profou ndly reduced. These findings agreed with those obtained in IL4-deficie nt mice(8,9) or using antibodies to IL-4(10) and the IL-4 receptor(11) . We conclude that Stat6 plays a central role in exerting IL-4-mediate d biological responses.