Role for NLRP1a inflammasome unravelled

The ligands and function of the NOD-, LRR- and pyrin domain-containing 1 (NLRP1) inflammasome have remained largely obscure. Now, studies in mice with an activating mutation in the gene encoding NLRP1a (termed Nlrp1a^Q593P/Q593P mice) have revealed that the NLRP1a inflammasome assembles in an ASC-independent manner to promote caspase 1-dependent production of interleukin-1β (IL-1β). Nlrp1a^Q593P/Q593P mice have neutrophilia and lethal systemic inflammation, and IL-18 or T cells partially suppressed this NLRP1a inflammasome-mediated inflammation. By contrast, Nlrp1a^Q593P/Q593PIl1b^−/− mice showed no signs of inflammatory disease but had caspase 1-dependent defects in the number and function of haematopoietic progenitor cells. Strikingly, NLRP1a activation as a result of the chemoablation or viral infection of haematopoietic cells led to progenitor cell death by pyroptosis and thus impaired haematopoiesis.