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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
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).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/380627a0
This article is cited by
-
Paedoksan ameliorates allergic disease through inhibition of the phosphorylation of STAT6 in DNCB-induced atopic dermatitis like mice
Applied Biological Chemistry (2023)
-
Efferocytosis is restricted by axon guidance molecule EphA4 via ERK/Stat6/MERTK signaling following brain injury
Journal of Neuroinflammation (2023)
-
Glucocorticoid activation of anti-inflammatory macrophages protects against insulin resistance
Nature Communications (2023)
-
The Impact of Air Pollution on Atopic Dermatitis
Current Allergy and Asthma Reports (2023)
-
The STAT6 inhibitor AS1517499 reduces the risk of asthma in mice with 2,4-dinitrochlorobenzene-induced atopic dermatitis by blocking the STAT6 signaling pathway
Allergy, Asthma & Clinical Immunology (2022)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
