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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References
Paul, W. E. Blood 77, 1859–1870 (1991).
Keegan, A. D. et al. Cell 76, 811–820 (1994).
Pernis, A. et al. Proc. natn. Acad. Sci. U.S.A. 92, 7971–7975 (1995).
Kotanides, H., Moczygemba, M., White, M. F. & Reich, N. C. J. biol. Chem. 270, 19481–19486 (1995).
Hou, J. et al. Science 265, 1701–1706 (1994).
Quelle, F. W. et al. Molec. cell. Biol. 15, 3336–3343 (1995).
Sun, X. J. et al. Nature 377, 173–177 (1995).
Kuhn, R., Rajewsky, K. & Muller, W. Science 254, 707–710 (1991).
Kopf, M. et al. Nature 362, 245–248 (1993).
Finkelman, F. D. et al. Proc. natn. Acad. Sci. U.S.A. 83, 9765–9769 (1986).
Finkelman, F. D. et al. A. Rev. Immun. 8, 303–333 (1990).
Conrad, D. H. et al. J. Immun. 141, 1091–1097 (1988).
Yokota, A. et al. Cell 55, 611–618 (1988).
Kikutani, H. et al. Cell 47, 657–665 (1986).
Noelle, A. et al. Proc. natn. Acad. Sci. U.S.A. 81, 6149–6153 (1984).
Roehm, N. W. et al. J. exp. Med. 160, 679–694 (1984).
Rabin, E. M., Ohara, J. & Paul, W. E. Proc. natn. Acad. Sci. U.S.A. 82, 2935–2939 (1985).
Rabin, E. M., Mond, J. J., Ohara, J. & Paul, W. E. J. exp. Med. 164, 517–531 (1986).
Hu-Li, J. et al. J. exp. Med. 165, 157–172 (1987).
Mossmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. & Coffman, R. L. J. Immun. 136, 2348–2357 (1986).
Street, N. E. et al. J. Immun. 144, 1629–1639 (1990).
Rothman, P. Res. Immun. 144, 579–583 (1993).
Keegan, A. D., Nelms, K., Wang, L. M., Pierce, J. H. & Paul, W. E. Immun. Today 15, 423–432 (1994).
Lin, J. X. et al. Immunity 2, 331–339 (1995).
Wang, L. M. et al. EMBO J. 11, 4899–4908 (1992).
Wang, L. M. et al. Science 261, 1591–1594 (1993).
Fujii, H. et al. Proc. natn. Acad. Sci. U.S.A. 92, 5482–5486 (1995).
Tanaka, T. et al. Cell 80, 353–361 (1995).
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Takeda, K., Tanaka, T., Shi, W. et al. Essential role of Stat6 in IL-4 signalling. Nature 380, 627–630 (1996). https://doi.org/10.1038/380627a0
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DOI: https://doi.org/10.1038/380627a0
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