Essential role of Stat6 in IL-4 signalling (original) (raw)

Nature volume 380, pages 627–630 (1996) Cite this article

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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Authors and Affiliations

  1. Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, Osaka, 565, Japan
    Kiyoshi Takeda, Takashi Tanaka, Wei Shi, Makoto Matsumoto, Masashi Minami & Shizuo Akira
  2. Osaka University Medical School, Department of Medicine III, 2-2 Yamada-oka, Suita, Osaka, 565, Japan
    Kiyoshi Takeda & Tadamitsu Kishimoto
  3. Department of Immunology and Medical Zoology, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, Hyogo, 663, Japan
    Shin-ichiro Kashiwamura & Kenji Nakanishi
  4. Research Institute, Osaka Medical Center of Maternal and Child Health, 840 Murodocho, Izumi, Osaka, 590-02, Japan
    Nobuaki Yoshida

Authors

  1. Kiyoshi Takeda
  2. Takashi Tanaka
  3. Wei Shi
  4. Makoto Matsumoto
  5. Masashi Minami
  6. Shin-ichiro Kashiwamura
  7. Kenji Nakanishi
  8. Nobuaki Yoshida
  9. Tadamitsu Kishimoto
  10. Shizuo Akira

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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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