Structure and Function of Inflammasomes

Upon stimulation by microbial or danger signals, large protein complexes called inflammasomes are assembled to activate caspase-1 and release proinflammatory cytokines, such as IL-1β, IL-18, as well as trigger pyroptotic cell death. In canonical inflammasome signaling, inflammasome assembly requires an upstream sensor including NLRP3, AIM2, an adaptor ASC, and a downstream effector pro-caspase-1. Inflammasome activation and assembly rely on homotypic interactions through PYD domains and CARD domains. In non-canonical inflammasome signaling, the caspase substrate gasdermin family play critical functions in pyroptotic cell death. The cleavage products of GSDMD by caspase-11 form membrane pore and trigger pyroptotic cell death.

We are particularly interested in the process of inflammasome assembly, activation and downstream signaling in canonical as well as non-canonical inflammasomes.