| First Author | Zhang L | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 4225 |
| PubMed ID | 30315153 | Mgi Jnum | J:268336 |
| Mgi Id | MGI:6268069 | Doi | 10.1038/s41467-018-06455-z |
| Citation | Zhang L, et al. (2018) POH1 deubiquitinates pro-interleukin-1beta and restricts inflammasome activity. Nat Commun 9(1):4225 |
| abstractText | Inflammasome activation is essential for host defence against invading pathogens, but is also involved in various forms of inflammatory diseases. The processes that control inflammasome activity are thus important for averting excessive immune responses and tissue damage. Here we show that the deubiquitinase POH1 negatively regulates the immune response triggered by inflammasome activation. POH1 deficiency in macrophages enhances mature IL-1beta production without significant alterations in inflammasome priming and ASC-caspase-1 activation. In WT macrophages, POH1 interacts with and deubiquitinates pro-IL-1beta by decreasing the K63-linked polyubiquitin chains, as well as decreases the efficacy of pro-IL-1beta cleavage. Furthermore, myeloid cell-specific deletion of POH1 aggravates lipopolysaccharide-induced systemic inflammation and alum-induced peritonitis inflammatory responses in vivo. Our study thereby reveals that POH1-mediated deubiquitination of pro-IL-1beta is an important regulatory event that restrains inflammatory responses for the maintenance of immune homeostasis. |
