IRF2 induces gasdermin D for pyroptosis

Abstract

Immunology Inflammasome activation triggers the cleavage of the protein gasdermin D. The N-terminal fragments oligomerize and form pores in the plasma membrane, leading to the release of the inflammatory cytokine interleukin-1β (IL-1β) and cell death by pyroptosis. Kayagaki et al. found that loss of the transcriptional regulator IRF2 reduced gasdermin D levels in mice and in human cells, resulting in decreases in IL-1β secretion and pyroptosis in response to inflammasome activation. Thus, like gasdermin D, IRF2 might also be a therapeutic target for the treatment of sepsis and other inflammasome-mediated diseases. Sci. Signal. 12 , eaax4917 (2019).