| First Author | Humphries F | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 1560 |
| PubMed ID | 29674674 | Mgi Jnum | J:265431 |
| Mgi Id | MGI:6158221 | Doi | 10.1038/s41467-018-03669-z |
| Citation | Humphries F, et al. (2018) The E3 ubiquitin ligase Pellino2 mediates priming of the NLRP3 inflammasome. Nat Commun 9(1):1560 |
| abstractText | The NLRP3 inflammasome has an important function in inflammation by promoting the processing of pro-IL-1beta and pro-IL-18 to their mature bioactive forms, and by inducing cell death via pyroptosis. Here we show a critical function of the E3 ubiquitin ligase Pellino2 in facilitating activation of the NLRP3 inflammasome. Pellino2-deficient mice and myeloid cells have impaired activation of NLRP3 in response to toll-like receptor priming, NLRP3 stimuli and bacterial challenge. These functions of Pellino2 in the NLRP3 pathway are dependent on Pellino2 FHA and RING-like domains, with Pellino2 promoting the ubiquitination of NLRP3 during the priming phase of activation. We also identify a negative function of IRAK1 in the NLRP3 inflammasome, and describe a counter-regulatory relationship between IRAK1 and Pellino2. Our findings reveal a Pellino2-mediated regulatory signaling system that controls activation of the NLRP3 inflammasome. |
