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Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted State6 gene

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Abstract

SIGNAL transducers and activators of transcription (Stats) are activated by tyrosine phosphorylation in response to cytokines, and are thought to mediate many of their functional responses1–4. Stat6 is activated in response to interleukin (IL)-4 (refs 5,6) and may contribute to various functions including mitogenesis, T-helper cell differentiation and immunoglobulin i so type switching7. To evaluate the role of Stat6, we generated Stat6-null mice (Stat6-l-) by gene disruption in embryonic stem cells. The mice were viable, indicating the lack of a non-redundant function in normal development. Although naive lymphoid cell development was normal, Stat6-l- mice were deficient in IL-4-mediated functions including Th2 helper T-cell differentiation, expression of cell surface markers, and immunoglobulin class switching to IgE. In contrast, IL-4-mediated proliferation was only partly affected.

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Authors and Affiliations

  1. Departments of Biochemistry, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38105, USA

    Kazuya Shimoda, Frederick W. Quelle, Tetsuya Nosaka & J. N. Ihle

  2. Department of Genetics, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38105, USA

    Jan van Deursent, P. C. Doherty & G. Grosveld

  3. Department of Immunology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38105, USA

    Mark Y. Sangster, Sally R. Sarawar, Richard T. Carson, Ralph A. Tripp & Dario A. A. Vignali

  4. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Charles Chu & W. E. Paul

Authors
  1. Kazuya Shimoda
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  2. Jan van Deursent
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  3. Mark Y. Sangster
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  4. Sally R. Sarawar
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  5. Richard T. Carson
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  6. Ralph A. Tripp
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  7. Charles Chu
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  8. Frederick W. Quelle
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  9. Tetsuya Nosaka
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  10. Dario A. A. Vignali
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  11. P. C. Doherty
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  12. G. Grosveld
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  13. W. E. Paul
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  14. J. N. Ihle
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Shimoda, K., van Deursent, J., Sangster, M. et al. Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted State6 gene. Nature 380, 630–633 (1996). https://doi.org/10.1038/380630a0

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  • DOI: https://doi.org/10.1038/380630a0

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