Other
14 Authors
- Lipkowitz S,
- Zhang J,
- Li Z,
- Zhao Y,
- Qiao G,
- Penninger JM,
- Liang Y,
- Ying H,
- Langdon WY,
- Shen H,
- Solway J,
- Tao E,
- Guo H,
- Chiang YJ
| First Author | Qiao G | Year | 2014 |
| Journal | Cell Rep | Volume | 6 |
| Issue | 4 | Pages | 709-23 |
| PubMed ID | 24508458 | Mgi Jnum | J:273983 |
| Mgi Id | MGI:6274203 | Doi | 10.1016/j.celrep.2014.01.012 |
| Citation | Qiao G, et al. (2014) E3 ubiquitin ligase Cbl-b suppresses proallergic T cell development and allergic airway inflammation. Cell Rep 6(4):709-23 |
| abstractText | E3 ubiquitin ligase Cbl-b has emerged as a gatekeeper that controls the activation threshold of the T cell antigen receptor and maintains the balance between tolerance and autoimmunity. Here, we report that the loss of Cbl-b facilitates T helper 2 (Th2) and Th9 cell differentiation in vitro. In a mouse model of asthma, the absence of Cbl-b results in severe airway inflammation and stronger Th2 and Th9 responses. Mechanistically, Cbl-b selectively associates with Stat6 upon IL-4 ligation and targets Stat6 for ubiquitination and degradation. These processes are heightened in the presence of T cell receptor (TCR)/CD28 costimulation. Furthermore, we identify K108 and K398 as Stat6 ubiquitination sites. Intriguingly, introducing Stat6 deficiency into Cblb(-/-) mice abrogates hyper-Th2 responses but only partially attenuates Th9 responses. Therefore, our data reveal a function for Cbl-b in the regulation of Th2 and Th9 cell differentiation. |
