Grail controls Th2 cell development by targeting STAT6 for degradation

Anupama Sahoo, Andrei Alekseev, Lidiya Obertas, Roza Nurieva

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish (US)
Article number4732
JournalNature communications
Volume5
DOIs
StatePublished - Aug 22 2014

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

MD Anderson CCSG core facilities

  • Genetically Engineered Mouse Facility
  • Research Animal Support Facility

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