POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity

Nat Commun. 2018 Oct 12;9(1):4225. doi: 10.1038/s41467-018-06455-z.


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-1β production without significant alterations in inflammasome priming and ASC-caspase-1 activation. In WT macrophages, POH1 interacts with and deubiquitinates pro-IL-1β by decreasing the K63-linked polyubiquitin chains, as well as decreases the efficacy of pro-IL-1β 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-1β is an important regulatory event that restrains inflammatory responses for the maintenance of immune homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Computer Systems
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Inflammasomes / drug effects
  • Inflammasomes / metabolism*
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Interleukin-1beta / metabolism*
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plasmids / genetics
  • Polyubiquitin / metabolism
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharides
  • PSMD14 protein, mouse
  • Trans-Activators
  • Polyubiquitin
  • Caspase 1
  • Proteasome Endopeptidase Complex