| First Author | Sahoo A | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 4732 | PubMed ID | 25145352 |
| Mgi Jnum | J:244869 | Mgi Id | MGI:5913648 |
| Doi | 10.1038/ncomms5732 | Citation | Sahoo A, et al. (2014) Grail controls Th2 cell development by targeting STAT6 for degradation. Nat Commun 5:4732 |
| abstractText | 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 alpha-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. |
