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. 2021 Dec 15;219(1):e20211405. doi: 10.1084/jem.20211405

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© 2021 Bauernfried and Hornung

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Figure 1. — NLRP1 inflammasome activation and its downstream signaling pathway. (A) Overview of the domain structure of human NLRP1 and mouse NLRP1B. (B) Overview of human NLRP1 activation by the DPP8/9 inhibitor VbP. (1) Generation of NLRP1^A and NLRP1^B by homeostatic degradation and assembly of the ternary DPP9-NLRP1^A-NLRP1^B complex. (2) Direct displacement of NLRP1^B from the DPP9 substrate tunnel leads to release of the C-terminal UPA-CARD fragments and (3) generation of an inflammasome seed. (4) Via the adaptor ASC, caspase-1 is activated. (5) Caspase-1 cleaves its substrates pro–IL-1β, which matures to pro-inflammatory IL-1β, and GSDMD, which (6) generates pores into the membrane and leads to a pyroptotic cell death.