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Grail controls Th2 cell development by targeting STAT6 for degradation

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  • Anupama Sahoo

    (M. D. Anderson Cancer Center)

  • Andrei Alekseev

    (M. D. Anderson Cancer Center)

  • Lidiya Obertas

    (M. D. Anderson Cancer Center)

  • Roza Nurieva

    (M. D. Anderson Cancer Center)

Abstract

T helper (Th)-2 cells are the major players in allergic asthma; however, the mechanisms that control Th2-mediated inflammation are poorly understood. Here we find that enhanced expression of Grail, an E3 ubiquitin ligase, in Th2 cells depends on interleukin (IL)-4-signalling components, signal transducer and activator of transcription 6 (Stat6) and Gata3, that bind to and transactivate the Grail promoter. Grail deficiency in T cells leads to increased expression of Th2 effector cytokines in vitro and in vivo and Grail-deficient mice are more susceptible to allergic asthma. Mechanistically, the enhanced effector function of Grail-deficient Th2 cells is mediated by increased expression of Stat6 and IL-4 receptor α-chain. Grail interacts with Stat6 and targets it for ubiquitination and degradation. Thus, our results indicate that Grail plays a critical role in controlling Th2 development through a negative feedback loop.

Suggested Citation

  • Anupama Sahoo & Andrei Alekseev & Lidiya Obertas & Roza Nurieva, 2014. "Grail controls Th2 cell development by targeting STAT6 for degradation," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5732
    DOI: 10.1038/ncomms5732
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